scholarly journals Role of the major histocompatibility complex in T cell activation of B cell subpopulations. lyb-5(+) and lyb-5(-) B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition

1981 ◽  
Vol 154 (2) ◽  
pp. 501-516 ◽  
Author(s):  
A Singer ◽  
PJ Morrissey ◽  
KS Hathcock ◽  
A Ahmed ◽  
I Scher ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Recognition ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Cell Subpopulations

This report has examined the requirements for T helper (T(H)) cell recognition of major histocompatibility complex (MHC) determinants expressed by B cells for the activation of unprimed Lyb-5(+) and Lyb-5(-) B cell subpopulations . The generation of primary T(H) cell-dependent plaque-forming cell responses in vitro microculture required the presence of Lyb-5(+) B cells because B cell populations that were deprived, either genetically or serologically, of the Lyb-5(+) subpopulation were not activated in these responses. Cell-mixing experiments in which A X B {arrow} A chimeric T(H) cells were mixed with purified populations of parental accessory cells and parental B cells demonstrated that the in vitro activation of Lyb-5(+) B cells did not require T(H) cell recognition of B cell MHC determinants, although it did require T(H) cell recognition of accessory cell MHC determinants . In contrast to the failure of Lyb-5(-) B cells to be activated in primary T(H) cell-dependent responses in vitro microculture, isolated populations of Lyb-5(-) B cells were triggered by T(H) cells in vivo in short-term adoptive transfer experiments . By the use of A X B {arrow} A chimeric T(H) cells and parental strain B adoptive hosts, it was possible in vivo to distinguish genetically restricted T(H) cell recognition of B cells from genetically restricted T(H) cell recognition of accessory cells. Similar to the results obtained in vitro, the activation in vivo of unfractionated (Lyb-5(+) plus Lyb-5(-)) B cell populations did not require T(H) cell recognition of B cell MHC determinants . In contrast, in the same in vivo responses activation of isolated populations of Lyb-5(-) B cells did require T(H) cell recognition of B cell MHC determinants. The most straightforward interpretation of these experiments is that T(H) cell recognition of B cell MHC determinants is required for the activation of Lyb-5(-) B cells but is not required for the activation of Lyb-5(+) B cells . To better understand why T(H) cell activation of one B cell subpopulation is genetically restricted, whereas activation of another subpopulation is not, the response of Lyb-5(+) and Lyb-5(-) B cells to the soluble activating factors present in concanavalin A-induced spleen cell supernates (Con A SN) was examined. It was observed that Lyb-5(-) B cells, as opposed to Lyb-5(+) B cells, were unable to respond in microculture to the nonspecific T(H) cell- activating factors present in Con A SN, even though they were able to nonspecifically respond under the same conditions to trinitrophenyllipopolysaccharide. It was observed that the ability of B cell subpopulations to respond to nonspecific soluble T cell factors paralleled their ability to be activated by T(H) cells in a genetically unrestricted manner. Thus, the present experiments demonstrate that activation by T(H) cells of Lyb-5(-) B cells is MHC restricted, whereas activation of Lyb-5(+) B cells is not. These experiments suggest that one possible explanation for such differences is that activation of Lyb-5(+) B cells does not require direct interaction with T(H) cells because they can be activated by soluble activation signals that T(H) cells secrete.

scholarly journals Role of the major histocompatibility complex in T cell activation of B cell subpopulations. Major histocompatibility complex-restricted and -unrestricted B cell responses are mediated by distinct B cell subpopulations

1981 ◽  
Vol 154 (4) ◽  
pp. 1100-1115 ◽  
Author(s):  
Y Asano ◽  
A Singer ◽  
RJ Hodes
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Recognition ◽  
Major Histocompatibility ◽  
T Cell Recognition ◽  
Histocompatibility Complex ◽  
Cell Subpopulations

The present study has evaluated the identity of the B cell subpopulations participating in T dependent antibody responses that differ in their requirements for major histocompatibility complex-restricted T cell recognition. In vitro responses of keyhole limpet hemocyanin (KLH)-primed T cells and trinitrophenyl (TNP)-primed B cells were studied to both low and high concentrations of the antigen TNP-KLH. It was first demonstrated that for responses to low concentrations of TNP-KLH, (A × B)F(1) {arrow} parent(A) chimeric helper T cells were restricted in their ability to recognize parent(A) but not parent(B) H-2 determinants expressed by both B cells and antigen-presenting cells (APC). In contrast, at higher antigen concentrations, helper T cells were not restricted in their interaction with B cells. It was then determined whether these observed differences in T cell recognition resulted from the activation of distinct B cell subpopulations with different activation requirements. At low concentrations of TNP-KLH it was demonstrated that Lyb-5(-) B cells were activated, and that it was thus the activation of the Lyb-5(-) subpopulation that required T cell recognition of B cell H-2 under these conditions. In contrast, responses to high concentration of antigen required the participation of Lyb-5(+) B cells, and these Lyb-5(+) B cells were activated by a pathway that required H-2- restricted T cell interaction with APC, but not with B cells. The findings presented here have demonstrated that Lyb-5(-) and Lyb-5(+) B cells constitute B cell subpopulations that differ significantly in their activation requirements for T cell-dependent antibody responses to TNP-KLH. In so doing, these findings have established that the function of genetic restrictions in immune response regulation is critically dependent upon the activation pathways employed by functionally distinct subpopulations of B, as well as T, lymphocytes.

scholarly journals A MOUSE B-CELL ALLOANTIGEN DETERMINED BY GENE(S) LINKED TO THE MAJOR HISTOCOMPATIBILITY COMPLEX

1973 ◽  
Vol 138 (6) ◽  
pp. 1289-1304 ◽  
Author(s):  
David H. Sachs ◽  
James L. Cone
Keyword(s):  
Major Histocompatibility Complex ◽  
Lymph Node ◽  
T Cell ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Surface Antigen ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Histocompatibility Complex

Antibodies cytotoxic for only a subpopulation of C57Bl/10 lymph node and spleen cells were detected when rat antiserum against B10.D2 was exhaustively absorbed with B10.A lymphocytes. Antibodies of similar specificity were also detected in B10.A anti-B10.D2 and in B10.A anti-C57Bl/10 alloantisera. Reactions with recombinant strains of mice indicate that the cell-surface antigen(s) responsible for this specificity is determined by gene(s) in or to the left of the Ir-1 region of the major histocompatibility complex. A variety of criteria implicate B cells as the subpopulation of lymphocytes bearing this antigen. In view of these data and the recent report by others of a T-cell alloantigen determined by gene(s) in the major histocompatibility complex, it seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes.

scholarly journals Major histocompatibility complex-restricted, polyclonal B cell responses resulting from helper T cell recognition of antiimmunoglobulin presented by small B lymphocytes.

1985 ◽  
Vol 161 (1) ◽  
pp. 223-241 ◽  
Author(s):  
H P Tony ◽  
D C Parker
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Lines ◽  
Major Histocompatibility ◽  
Helper T Cell ◽  
Histocompatibility Complex ◽  
T Cell Lines

Anti-Ig has been widely used as a model for antigen receptor-mediated B cell activation. B cells activated with mitogenic concentrations of anti-Ig (approximately 10 micrograms/ml) become responsive to a set of T cell-derived, antigen-nonspecific helper factors that enable the B cells to proliferate, and, in some cases, mature to Ig secretion. In the present experiments, we show that anti-Ig can also be used as a model for major histocompatibility complex (MHC)-restricted, antigen-specific T-B cell collaboration. We used murine helper T cell lines and T cell hybridomas specific for a protein antigen, the F(ab')2 fragment of normal rabbit IgG. Small B cells are very efficient at presenting rabbit anti-IgM or rabbit anti-IgD to these rabbit Ig-specific T cell lines and hybridomas, and the responding (initially) small B cells, appear to be the only antigen-presenting cells required. Efficient presentation depends upon binding of rabbit antibody to mIg on the B cell surface. MHC-restricted recognition of rabbit Ig determinants on the B cell surface results in a polyclonal B cell response. This response is qualitatively different from the well-studied response to blastogenic concentrations of anti-Ig plus stable, T cell-derived helper factors, since it (a) requires 1,000-fold lower concentrations of anti-Ig, (b) involves helper T cell functions other than, or in addition to, the local production of the same stable helper factors, and (c) is largely MHC-restricted at the T-B cell level.

scholarly journals A cloned major histocompatibility complex-restricted trinitrophenyl-reactive human helper T cell line that activates B cell subsets via two distinct pathways.

1983 ◽  
Vol 158 (5) ◽  
pp. 1444-1458 ◽  
Author(s):  
M A Principato ◽  
G S Thompson ◽  
S M Friedman
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Interleukin 2 ◽  
Major Histocompatibility ◽  
Helper T Cell ◽  
Histocompatibility Complex ◽  
B Cell Subsets

A cloned, trinitrophenyl (TNP)-specific helper T cell line (TCL), termed E-11, has been established in long-term, interleukin 2-dependent culture and used to study human T helper (Th)-B cell collaboration. Co-culture of E-11 with TNP-modified, but not unmodified or FITC-modified, autologous B cells results in a vigorous, polyclonally plaque-forming cell (PFC) response. E-11 helper activity is not constitutive, but requires antigen-specific, major histocompatibility complex-restricted activation of the TCL cells by interaction with TNP-modified autologous or DR 5+ allogeneic macrophages. Using B cell subsets isolated by discontinuous density gradient cengrifugation as responder populations, we determined that E-11 activates B cell subsets via two distinct mechanisms: (a) E-11 polyclonally activates large B cells in an unrestricted and nonspecific manner; and (b) E-11 preferentially induces a PFC response by TNP-modified small B cells. These results suggest that the large B cell subset is activated by helper signals generated during the Th-antigen-presenting cell interaction, while small B cells require an additional stimulus that is provided by antigen-specific Th-B cell contact.

scholarly journals Designer Glycopeptides for Cytotoxic T Cell–based Elimination of Carcinomas

2004 ◽  
Vol 199 (5) ◽  
pp. 707-716 ◽  
Author(s):  
Yanfei Xu ◽  
Sandra J. Gendler ◽  
Alessandra Franco
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Large Population ◽  
Vaccination Strategy ◽  
Cytotoxic T Cell ◽  
Major Histocompatibility ◽  
Carbohydrate Antigens ◽  
Histocompatibility Complex

Tumors express embryonic carbohydrate antigens called tumor-associated carbohydrate antigens (TACA). TACA-containing glycopeptides are appealing cytotoxic T cell (CTL)-based vaccines to prevent or treat cancer because the same sugar moieties are expressed in a variety of tumors, rendering a vaccination strategy applicable in a large population. Here we demonstrate that by using glycopeptides with high affinity for the major histocompatibility complex and glycosylated in a position corresponding to a critical T cell receptor (TcR) contact, it is possible to induce anti-TACA CTL in vivo. In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (β-Gal-[1→3]-α-GalNAc-O-serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. The fine specificity of the TF-specific CTL repertoire indicates that the TcR recognize the glycosylated amino acid residue together with TF in a conventional major histocompatibility complex class I–restricted fashion. These results have high potential for immunotherapy against a broad range of tumors.

scholarly journals Distinct structural compartmentalization of the signal transducing functions of major histocompatibility complex class II (Ia) molecules.

1994 ◽  
Vol 179 (2) ◽  
pp. 763-768 ◽  
Author(s):  
P André ◽  
J C Cambier ◽  
T K Wade ◽  
T Raetz ◽  
W F Wade
Keyword(s):  
Signal Transduction ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Mhc Class Ii ◽  
Cell Activation ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Class II major histocompatibility complex encoded proteins (MHC class II or Ia molecules) are principal plasma membrane proteins involved in activation of both B and T cells during antigen-driven immune responses. Recent data indicate that class II molecules are more than simply recognition elements that provide a ligand for the T cell antigen receptor. Changes in B cell physiology that follow class II binding are now recognized as being required not only for the induction of T cell activation, but also for B cell activation and proliferation. It is interesting to note that class II molecules appear to transduce signals via two distinct mechanisms depending upon the differentiative state of the B cell on which they are expressed. While one of these pathways, involving cAMP generation and protein kinase C localization in the cytoskeletal/nuclear compartment, is seen in resting B cells, the second is seen in primed B cells and involves tyrosine kinase activation, inositol lipid hydrolysis, and Ca2+ mobilization. Use of this pathway is correlated with ability of class II to transduce signals leading to B cell proliferation. To begin to address the molecular basis of this unique, activation-dependent, differential coupling of class II to signaling pathways, we conducted mutational analysis of class II structural requirements for signal transduction. Here we report that the cytoplasmic (Cy) domains of I-Ak class II molecules are not required for either receptor-mediated activation of protein tyrosine phosphorylation or Ca2+ mobilization. This is in contrast to the requirement of the Cy domain of beta chain of class II for the alternate signaling pathway and efficient antigen presentation to autoreactive T cell lines. Disparate distribution of functional motifs within the MHC class II molecules may reflect use of distinct receptor associated effector molecules to sustain different modes of signal transduction in various class II-expressing cells.

Immuno-informatics-based identification of novel potential B cell and T cell epitopes to fight Zika virus infections

2020 ◽  
Vol 20 ◽  
Author(s):  
Wahiba Ezzemani ◽  
Marc P. Windisch ◽  
Anass Kettani ◽  
Haya Altawalah ◽  
Jalal Nourlil ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
B Cell ◽  
Zika Virus ◽  
T Cell Epitopes ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Virus Infections ◽  
Histocompatibility Complex

Background: Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. Objective: In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. Methods: The prediction of the most antigenic epitopes has targeted the capsid and the envelope proteins as well as nonstructural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity were evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss-Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. Results: As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68 :01), ETLHGTVTV (HLA-A*68 :02), DENHPYRTW (HLA-B*44 :02),QEGVFHTMW (HLA-B*44 :03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02 :02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAETWFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11 :01), and DGCWYGMEIRPRKEP (HLA-DRB5*01:01). Conclusion : This study provides novel potential B cell and T cell epitopes to fight Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify the immunogenicity, safety of the predicted structure, and ultimately the vaccine properties to prevent ZIKV infections are warranted.

scholarly journals Antigen recognition by a T cell clone outside the context of the major histocompatibility complex. A role for Mls in antigen presentation.

1984 ◽  
Vol 159 (1) ◽  
pp. 305-312 ◽  
Author(s):  
S J Waters ◽  
S D Waksal ◽  
G P Norton ◽  
C A Bona
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Clone ◽  
Antigen Recognition ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Differentiation Markers ◽  
Histocompatibility Complex ◽  
T Cell Clone

A T cell clone isolated from antigen-primed CB6/F1 mice was shown to proliferate to keyhole limpet hemocyanin (KLH) in the presence of irradiated syngeneic F1 spleen cells, as well as spleen cells from either parental strain (BALB/c and C57BL/6). The genetic restriction involved in this antigen-specific proliferation was mapped using BXD (C57BL/6 X DBA/2) recombinant inbred strains of mice to the Mls gene on chromosome one. To exclude the role of Ia antigens as the restricting determinants, monoclonal anti-Ia antibodies were used to block the in vitro proliferative response of this clone. Although anti-Iab and anti-Iad blocked the proliferation of this clone to KLH in the presence of irradiated spleen cells from either parent, this effect was shown to be dependent on Ia molecules passively absorbed by the T cell clone from the irradiated filler cells. Since the T clone expressed Thy-1.2 and Lyt-1+ differentiation markers, its helper activity was compared with other KLH carrier-specific clones in an in vitro antibody synthesis assay. The Mls-KLH-restricted T cell clone, in contrast to other carrier-specific, major histocompatibility complex (MHC)-restricted T cell clones, was unable to cooperate with trinitrophenyl (TNP)-primed B cells in the presence of TNP-KLH to generate an anti-TNP response. These experiments suggest that non-MHC determinants, such as autologous Mls gene products, may play a role in genetically restricted antigen recognition by T lymphocytes.

Sign in / Sign up

Export Citation Format

Share Document