scholarly journals Epitopes associated with MHC restriction site of T cells. III. I-J epitope on MHC-restricted T helper cells.

1987 ◽  
Vol 166 (6) ◽  
pp. 1613-1626 ◽  
Author(s):  
Y Asano ◽  
T Nakayama ◽  
M Kubo ◽  
J Yagi ◽  
T Tada
Keyword(s):  
T Cells ◽  
Cell Function ◽  
Cell Receptor ◽  
Class Ii ◽  
Early Ontogeny ◽  
Th Cells ◽  
Mhc Restriction ◽  
Th Cell ◽  
Class Ii Mhc ◽  
Isomorphic Structure

I-J epitopes were found to be associated with the functional site of the class II MHC-restricted helper T (Th) cells: Virtually all of the H-2k-restricted Th cell function of H-2kxbF1 T cells was inhibited by the anti-I-Jk mAb, leaving the H-2b-restricted function unaffected. The I-Jk epitope was inducible in Th cells of different genotype origin according to the environmental class II antigens present in the early ontogeny of T cells. Although above results suggested that I-J is the structure reflecting the inducible MHC restriction specificity, further studies revealed some interesting controversies: First, the I-J phenotype did not always correlate with the class II restriction specificity, e.g., I-Ab-restricted Th from 5R was I-Jk-positive, whereas I-Ak-restricted Th of 4R was not. Second, there was no trans expression of parental I-J phenotypes and restriction specificities in F1 Th, e.g., the I-J phenotype was detected only on I-Ab-restricted Th of (4R X 5R)F1, whereas it was absent on I-Ak-restricted Th. This strict linkage between the restriction specificity and I-J phenotype was also found on Th cells developed in bone marrow chimera constructed with intra-H-2-recombinant mice. The expression of I-Jk was always associated with the restriction specificity of the relevant host. Thus, the restriction specificity of Th cells followed the host type, and the I-J expression on Th was exactly the same as that expressed by the host haplotype. These results indicate that I-J is an isomorphic structure adaptively expressed on Th cells that is involved in the unidirectional regulatory cell interactions, and that the polymorphism cannot be explained merely by the restriction specificity of the conventional T cell receptor heterodimer.

scholarly journals T cell regulation of B cell activation. Lyt-1+,2-T cells modify the MHC-restricted function of heterogeneous and cloned T suppressor cells.

1985 ◽  
Vol 162 (2) ◽  
pp. 413-426 ◽  
Author(s):  
Y Asano ◽  
R J Hodes
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Suppressor Cells ◽  
Effector Function ◽  
B Cell Activation ◽  
Experimental Conditions ◽  
Th Cells ◽  
Mhc Restriction

Previous studies have shown the existence of both heterogeneous Lyt-1-,2+ suppressor (Ts) cells and cloned Lyt-1+,2- Ts cells which, despite the difference in their Lyt phenotypes, functioned in a similar antigen-specific and major histocompatibility complex (MHC)-restricted fashion to suppress the antibody responses generated by cloned helper T (Th) cells and hapten-primed B cells. Our studies were carried out to assess in further detail the genetically restricted cell interactions that mediate this immune response suppression. We show that the activation of both heterogeneous and cloned Ts cells is antigen-specific and MHC-restricted under our experimental conditions. After appropriate activation, the effector function of both cloned Lyt-1+,2-Ts cells and heterogeneous Lyt-1-,2+ Ts cells was also antigen-specific. In contrast, once activated, Ts cells suppressed the responses generated by cloned Th cells and hapten-primed B cells in an MHC-unrestricted fashion. We also showed, however, that a population of unprimed Lyt-1+,2-T cells was able to significantly alter the genetic restriction requirements for Ts cell function. The activity of this population was itself MHC-restricted, and was observed only when the unprimed Lyt-1+,2-T cells shared the MHC restriction specificity of the cloned Th cells functioning in a given response. When these requirements were satisfied, Lyt-1+,2- T cells significantly modified the suppression mediated by both heterogeneous and cloned Ts cells, resulting in suppression that was then MHC restricted in its effector function as well as in its activation requirements. Thus, our findings suggest that the observed MHC restriction in Ts function is the result of a complex interaction involving Ts cells, Th cells, and an additional population of MHC-restricted Lyt-1+,2- T cells. This newly characterized activity of Lyt-1+,2- T cells functionally resembles that of an MHC-restricted contrasuppressor population that selectively blocks a pathway of MHC-unrestricted Ts activity, while leaving intact susceptibility to MHC-restricted Ts effects.

scholarly journals MHC-restricted minimal regulatory circuit initiated by a class II-autoreactive T cell clone.

1987 ◽  
Vol 165 (5) ◽  
pp. 1284-1295 ◽  
Author(s):  
K Sano ◽  
I Fujisawa ◽  
R Abe ◽  
Y Asano ◽  
T Tada
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Class Ii ◽  
Secondary Antibody ◽  
Th Cells ◽  
Mhc Restriction ◽  
Autoreactive T Cell ◽  
Regulatory Circuit ◽  
T Cell Clone

The in vivo administration of a self-class II-reactive Th clone MS202 derived from C3H into syngeneic mice resulted in the suppression of both primary and early secondary antibody responses against T cell-dependent antigens. The suppression was due to the generation of antigen-nonspecific Ts cells in the recipient, as the splenic T cells from the mice treated with MS202 were able to strongly suppress the in vitro secondary antibody response of primed syngeneic spleen cells. The dose-response curve of suppression indicated the generation of an effector type Ts that directly suppressed Th. The surface phenotype of Ts was Ly-1+,2-, L3T4+, I-J-. The presence of Ly-1+,2+ T cells was not required to induce the suppression. The suppression was strictly restricted to H-2k, as F1 Ts cells were able to suppress the response of C3H but not of B6 B cells helped by the same F1 Th cells. The experiments with chimeric mice indicated that the direct target of Ts is an MHC-restricted Th but not a B cell or APC. The results indicate the existence of a minimal regulatory circuit where an MHC-restricted Th induces a preprogrammed Ts that in turn directly suppresses Th with the same MHC-restriction specificity. The induction of and suppression by Ts appeared to be due to the direct recognition of MHC restriction sites of Th cells.

scholarly journals CD4+ Th Cells Resembling Regulatory T Cells That Inhibit Chronic Colitis Differentiate in the Absence of Interactions Between CD4 and Class II MHC

2003 ◽  
Vol 171 (5) ◽  
pp. 2279-2286 ◽  
Author(s):  
Timothy L. Denning ◽  
Hai Qi ◽  
Rolf König ◽  
Kevin G. Scott ◽  
Makoto Naganuma ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Class Ii ◽  
Chronic Colitis ◽  
Th Cells ◽  
Class Ii Mhc

scholarly journals Follicular lymphoma tumor–infiltrating T-helper (TH) cells have the same polyfunctional potential as normal nodal TH cells despite skewed differentiation

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3591-3602 ◽  
Author(s):  
Shannon P. Hilchey ◽  
Alexander F. Rosenberg ◽  
Ollivier Hyrien ◽  
Shelley Secor-Socha ◽  
Matthew R. Cochran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Follicular Lymphoma ◽  
Critical Role ◽  
Cell Receptor ◽  
Effector Memory ◽  
T Helper ◽  
Th Cells ◽  
Lineage Differentiation ◽  
Th Cell

Abstract The follicular lymphoma (FL) T-cell microenvironment plays a critical role in the biology of this disease. We therefore determined the lineage, differentiation state, and functional potential of FL-infiltrating CD4+ T-helper cells (TH) compared with reactive and normal lymph node (NLN) TH cells. Relative to NLNs, FL cells have decreased proportions of naive and central memory but increased proportions of effector memory TH cells. We further show differences in the distribution and anatomical localization of CXCR5+ TH populations that, on the basis of transcription factor analysis, include both regulatory and follicular helper T cells. On Staphylococcus enterotoxin-B stimulation, which stimulates T cells through the T-cell receptor, requires no processing by APCs, and can overcome regulator T cell-mediated suppression, the proportion of uncommitted primed precursor cells, as well as TH2 and TH17 cells is higher in FL cells than in reactive lymph nodes or NLNs. However, the proportion of TH1 and polyfunctional TH cells (producing multiple cytokines simultaneously) is similar in FL cells and NLNs. These data suggest that, although TH-cell differentiation in FL is skewed compared with NLNs, FL TH cells should have the same intrinsic ability to elicit antitumor effector responses as NLN TH cells when tumor suppressive mechanisms are attenuated.

scholarly journals The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells.

1992 ◽  
Vol 176 (1) ◽  
pp. 47-58 ◽  
Author(s):  
D Vremec ◽  
M Zorbas ◽  
R Scollay ◽  
D J Saunders ◽  
C F Ardavin ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Magnetic Beads ◽  
Cell Receptor ◽  
Class Ii ◽  
Immunofluorescent Staining ◽  
Alpha Chain ◽  
Class Ii Mhc ◽  
Antigen Presenting

A new procedure for rapid isolation of dendritic cells (DC) was devised, involving collagenase digestion of tissues, dissociation of lymphoid-DC complexes, selection of light-density cells, then depletion of lymphocytes and other non-DC by treatment with a mixture of lineage-specific monoclonal antibodies (mAbs) and removal with anti-immunoglobulin-coupled magnetic beads. This enriched population (approximately 80% DC) was further purified when required by fluorescence-activated cell sorting for cells expressing high levels of class II major histocompatibility complex (MHC). The isolated DC were characterized by immunofluorescent staining using a panel of 30 mAbs. Thymic DC were surface positive for a number of markers characteristic of T cells, but they were distinct from T-lineage cells in expressing high levels of class II MHC, in lacking expression of the T cell receptor (TCR)-CD3 complex, and having TCR beta and gamma genes in germline state. Splenic DC shared many markers with thymic DC, but were negative for most T cell markers, with the exception of CD8. A substantial proportion of DC from both thymus and spleen expressed CD8 at high levels, comparable with that on T cells. This appeared to be authentic CD8, and was produced by the DC themselves, since they contained CD8 alpha mRNA. Thymic DC presented both the CD8 alpha and beta chains on the cell surface (Ly-2+3+), although the alpha chain was in excess; the splenic DC expressed only the CD8 alpha chain (Ly-2+3-). It is suggested that the expression of CD8 could endow certain antigen-presenting DC with a veto function.

scholarly journals Maturational arrest from CD4+8+ to CD4+8- thymocytes in a mutant strain (LEC) of rat.

1990 ◽  
Vol 172 (6) ◽  
pp. 1615-1624 ◽  
Author(s):  
T Agui ◽  
M Oka ◽  
T Yamada ◽  
T Sakai ◽  
K Izumi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mutant Strain ◽  
Cell Subset ◽  
Cell Receptor ◽  
Class Ii ◽  
Class Ii Mhc ◽  
Normal Expression ◽  
Lec Rats ◽  
T Cell Maturation

A mutant strain (LEC) of rats was found to have a novel defect in T cell maturation, that is, arrest of differentiation from CD4+8+ to CD4+8- but not to CD4-8+ thymocytes. FACS analyses demonstrated a deficiency in the CD4+8- T cell subset in the thymus and a marked decrease in CD4+ T cells in peripheral lymphoid organs. Expression of the T cell receptor (TCR)/CD3 complex in CD4+8+ and CD4-8+ thymocytes of LEC rats was normal. Expression of class II major histocompatibility complex (MHC) in the thymus of LEC rats was also the same as that of normal rats. These results indicate that maturational arrest occurs only in the transition pathway from CD4+8+ to CD4+8- thymocytes, and that this mutation can not be attributed to the default of expression of either TCR/CD3, CD4, or class II MHC antigen. Consequently, dysfunction of helper T cells was observed in LEC rats, while killer T cells and B cells functioned normally. Although the complete identification of the origin of this mutation requires further studies, it is hoped that such investigations will throw light on the mechanism of positive selection.

scholarly journals Positive and Negative Selection in Transgenic Mice Expressing a T-Cell Receptor Specific for Influenza Nucleoprotein and Endogenous Superantigen

1993 ◽  
Vol 3 (3) ◽  
pp. 159-174 ◽  
Author(s):  
Clio Mamalaki ◽  
James Elliott ◽  
Trisha Norton ◽  
Nicholas Yannoutsos ◽  
Alain R. Townsend ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class Ii ◽  
Cytotoxic T Cell ◽  
Dependent Manner ◽  
Class Ii Mhc ◽  
Peripheral T Cells

A transgenic mouse was generated expressing on most (>80%) of thymocytes and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5). This clone is CD8+and recognizes αα366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class ,MHC Db(Townsend et al., 1986). The receptor utilizes the Vβ11 and Vα4 gene segments for the β chain and α chain, respectively (Palmer et al., 1989). The usage of Vβ11 makes this TcR reactive to Class II IE molecules and an endogenous ligand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the development of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MHC IE (e.g., CBA/Ca H-2kand BALB/c H-2d) and the endogenous Mtv ligands. Positive selection of CD8+T cells expressing the Vβ11 is seen in C57BL/10 transgenic mice (H-2b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner after a period ofin vitroculture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-positive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8+peripheral T-cells in these (H-2kor H-2d) F5 mice are predominantly Vβ11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even following backcrossing of the F5 TcR transgene to H-2dscid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chain genes is impaired.

scholarly journals Epitopes associated with the MHC restriction site of T cells. II. Somatic generation of Iat epitopes on T cells in radiation bone marrow chimeras.

1987 ◽  
Vol 165 (1) ◽  
pp. 87-96 ◽  
Author(s):  
Y Asano ◽  
T Tada
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Restriction Site ◽  
Cell Receptor ◽  
Th Cells ◽  
Mhc Restriction ◽  
Physiologic Condition ◽  
Bone Marrow Chimeras

We described in this paper systematic alterations in the expression of unique I region controlled epitopes on helper T cells (Th) in chimeras according to the changes in their H-2 restriction specificity. Taking advantage of the reactivity of monoclonal antibodies (anti-Iat) putatively specific for the epitopes indirectly controlled by I region and expressed in association with the Iak restriction site of Th, we examined the alterations of these epitopes on Th cells from various bone marrow chimeras. Iatk epitopes were physiologically expressed on Iak-restricted but not on Iab-restricted Th cells in (H-2k X H-2b)F1 mice. In the chimeric condition, the H-2k-restricted Th of B6----F1 chimera acquired the expression of Iatk even though B6 Th is unable to express Iatk when developed under the physiologic condition. Iatk are also found on Th of fully allogeneic chimera of B6----C3H, whereas Th cells of C3H----B6 completely lost the Iatk expression. These results indicate that Iat epitopes originally defined as unique I region-controlled determinants selectively expressed on T cells are not encoded by the I region genes but are associated with the T cell receptor that sees the self Ia. The epitopes undergo the adaptive alterations according to the acquisition of a new MHC restriction. This is the first example to demonstrate the epitope associated with T cell receptor which undergo the systematic adaptive differentiation.

MHC Sınıf I ve MHC Sınıf II Gen Düzenlenmesi

2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Gene Regulation ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Regulation Mechanisms

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription

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