scholarly journals Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex

1977 ◽  
Vol 146 (3) ◽  
pp. 828-843 ◽  
Author(s):  
A Yano ◽  
RH Schwartz ◽  
WE Paul
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Antigen Presentation ◽  
T Lymphocyte ◽  
Proliferative Response ◽  
Gene Products ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Histocompatibility Complex

A method is described for stimulating proliferation in primed populations of murine T lymphocytes using antigen bound to mitomycin-C-treated spleen cells. This form of antigen presentation appears to be an active process because heat-killed spleen cells are ineffective, and because genetic similarity at the major histocompatibility complex (MHC) between the responder T cells and the presenting spleen cells is required for effective interactions. At all times examined, from day 3 to day 6 of the proliferative response, syngeneic spleen cells presented antigen better to peritoneal exudate T-lymphocyte-enriched cells (PETLES) than semisyngeneic F(1) spleen cells, which in turn could present antigen better than totally allogeneic spleen cells. Spleen cell mixing experiments demonstrated that these genetic restrictions were not the result of suppression by the ongoing mixed lymphocyte reactions (MLR) in the allogeneic and F(1) cases. Furthermore, incompatibility at the Mls locus generated a strong MLR but failed to prevent antigen presentation if the spleen cells and PETLES were compatible. Genetic mapping studies demonstrated that compatibility at only the I-A subregion of the MHC was sufficient for effective presentation of the antigen, dinitrophenylated ovalbumin. Compatibility at only the K region, or the K and D regions was not sufficient. These results support the concept that functional activation of primed, proliferating T lymphocytes requires the participation of gene products coded for by the I region of the MHC. This conclusion is consistent with a growing body of evidence which suggests that most T cells recognize antigen in association with MHC gene products.

scholarly journals Antigen-specific T cell clones restricted to unique F(1) major histocompatibility complex determinants. Inhibition of proliferation with a monoclonal anti-Ia antibody

1981 ◽  
Vol 153 (3) ◽  
pp. 677-693 ◽  
Author(s):  
B Sredni ◽  
LA Matis ◽  
EA Lerner ◽  
WE Paul ◽  
RH Schwartz
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Proliferative Response ◽  
Cell Populations ◽  
Gene Products ◽  
Spleen Cells ◽  
Histocompatibility Complex ◽  
Cell Clones ◽  
Antigen Presenting

The existence of T cells specific for soluble antigens in association with unique F(1) or recombinant major histocompatibility complex (MHC) gene products was first postulated from studies on the proliferative response of whole T cell populations to the antigen poly(Glu(55)Lys(36)Phe(9))(n) (GLφ). In this paper we use the newly developed technology of T lymphocyte cloning to establish unequivocally the existence of such cells specific for GLφ and to generalize their existence by showing that F(1)- specific cells can be isolated from T cell populations primed to poly(Glu(60)Ala(30)Tyr(10))(n) (GAT) where such clones represent only a minor subpopulation of cells. Gl.4b-primed B10.A(5R) and GAT-primed (B10.A × B10)F(1) lymph node T cells were cloned in soft agar, and the colonies that developed were picked and expanded in liquid culture. The GLφ-specific T cells were then recloned under conditions of high-plating efficiency to ensure that the final colonies originated from single cells. T cells from such rigorously cloned populations responded to stimulation with GILφ but only in the presence of nonimmune, irradiated spleen cells bearing (B10.A × B10)F(1) or the syngeneic B 10.A(5R) recombinant MHC haplotype. Spleen cells from either the B10 or B 10.A parental strains failed to support a proliferative response, even when added together. (B10 × B10.D2)F(1) and (B10 × B10.RIII)F(1) spleen cells also supported a proliferative response but (B10 × B10.Q)F(1) and (B10 X B10.S)F(1) spleen cells did not. These results suggested that the T cell clones were specific for GL[phi} in association with the β(AE)(b)-α(E) (k,d,r,) Ia molecule and that recognition required both gene products to be expressed in the same antigen-presenting cells. Support for this interpretation was obtained from inhibition experiments using the monoclonal antibody Y-17 specific for a determinant on the β(AE)(b)-αE Ia molecule. Y-17 completely inhibited the proliferative response of a GLφ-specific clone but had no effect on the response of either a PPD-specific or GAT-specific clone, both of which required the β(A)-α(A) Ia molecule as their restriction element. No evidence could be found for the involvement of suppressor T cells in this inhibition. We therefore conclude that the phenomenon of F(1)-restricted recognition by proliferating T cells results from the presence of antigen- specific clones that must recognize unique F(1) or recombinant Ia molecules on the surface of antigen-presenting cells in addition to antigen in order to be stimulated.

scholarly journals Indirect allorecognition of platelets by T helper cells during platelet transfusions correlates with anti-major histocompatibility complex antibody and cytotoxic T lymphocyte formation [published erratum appears in Blood 1995 Dec 15;86(12):4710]

Blood ◽  
1995 ◽  
Vol 86 (2) ◽  
pp. 805-812 ◽  
Author(s):  
JW Semple ◽  
ER Speck ◽  
YP Milev ◽  
V Blanchette ◽  
J Freedman
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Nk Cell ◽  
Cytotoxic T Lymphocyte ◽  
Spleen Cells ◽  
Histocompatibility Complex ◽  
Platelet Transfusions

To study the cellular immunology of platelet-induced alloimmunization, a murine transfusion model was developed. BALB/c (H-2d) recipient mice were transfused weekly with 2 x 10(8) platelets or 10(3) leukocytes from C57BL/6 (H-2b) donor mice. Recipient antidonor major histocompatibility complex (MHC) class I alloantibodies could be detected in flow cytometric assays by the fifth platelet transfusion. In contrast, when leukocytes only were transfused, alloantibodies were not detected. In vitro assays demonstrated that murine H-2b platelets were positive for MHC class I expression but lacked MHC class II molecules on their membranes and were unable to stimulate proliferation or cytokine production when incubated with naive H-2d spleen cells. In vivo, however, platelet transfusions induced two distinct patterns of cell-mediated reactivity. First, during the initial transfusions and before alloantibody formation, there was induction of T-cell anergy, characterized by the inability of recipient T cells to respond to Concanavalin A (ConA) or to proliferate in an antidonor mixed lymphocyte reaction (MLR), together with suppressed natural killer (NK) cell activity. This unresponsiveness was associated with a transient increase in nitric oxide (NO)-dependent cytotoxicity and interleukin-1 (IL-1) production. Second, once alloantibodies developed, significantly increased antidonor CD8+ cytotoxic T lymphocyte (CTL) and NK cell responses were observed. At this time, when recipient spleen cells were depleted of CD8+ T cells and incubated with only donor platelets in 7- day antigen-presenting cell (APC) assays, enhanced proliferation and IL- 2 production occurred. These cellular responses were not seen when 10(3) allogeneic leukocytes were transfused. Thus, the results suggest that leukoreduced platelet transfusions induce antidonor MHC antibodies and CD8+ CTL responses in recipient mice. At the same time, the transfusions induced recipient CD4+ T-cell activation when incubated with donor platelets in the presence of syngeneic APCs, an indirect recognition pathway that correlates with the time of alloantibody production.

scholarly journals Presentation of numerous viral peptides to mouse major histocompatibility complex (MHC) class I-restricted T lymphocytes is mediated by the human MHC-encoded transporter or by a hybrid mouse-human transporter.

1993 ◽  
Vol 177 (6) ◽  
pp. 1785-1790 ◽  
Author(s):  
J W Yewdell ◽  
F Esquivel ◽  
D Arnold ◽  
T Spies ◽  
L C Eisenlohr ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Antigen Processing ◽  
Class I ◽  
Gene Products ◽  
Major Histocompatibility ◽  
Mouse Major Histocompatibility Complex ◽  
Histocompatibility Complex ◽  
Functional Complex ◽  
Human And Mouse

The major histocompatibility complex-encoded transporter associated with antigen processing (TAP) is required for the efficient presentation of cytosolic antigens to class I-restricted T cells. TAP is thought to be formed by the interaction of two gene products, termed TAP1 and TAP2. We find that TAPs consisting either of human subunits, or mouse TAP1 and human TAP2, facilitate the presentation of numerous defined viral peptides to mouse class I-restricted T cells. As human and mouse TAP2 and TAP1 differ in 23 and 28% of their residues, respectively, this indicates that TAP1 and TAP2 can form a functional complex with partners considerably different from those they coevolved with. Moreover, these findings indicate that widely disparate TAPs facilitate delivery of the same peptides to class I molecules. These findings suggest that TAP polymorphism does not greatly influence the types of peptides presented to the immune system.

scholarly journals Making the Most of Major Histocompatibility Complex Molecule Multimers: Applications in Type 1 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Greg S. Gojanovich ◽  
Paul R. Hess
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Subsets ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Pancreatic Islets Of Langerhans

Classical major histocompatibility complex (MHC) class I and II molecules present peptides to cognate T-cell receptors on the surface of T lymphocytes. The specificity with which T cells recognize peptide-MHC (pMHC) complexes has allowed for the utilization of recombinant, multimeric pMHC ligands for the study of minute antigen-specific T-cell populations. In type 1 diabetes (T1D), CD8+ cytotoxic T lymphocytes, in conjunction with CD4+ T helper cells, destroy the insulin-producingβcells within the pancreatic islets of Langerhans. Due to the importance of T cells in the progression of T1D, the ability to monitor and therapeutically target diabetogenic clonotypes of T cells provides a critical tool that could result in the amelioration of the disease. By administering pMHC multimers coupled to fluorophores, nanoparticles, or toxic moieties, researchers have demonstrated the ability to enumerate, track, and delete diabetogenic T-cell clonotypes that are, at least in part, responsible for insulitis; some studies even delay or prevent diabetes onset in the murine model of T1D. This paper will provide a brief overview of pMHC multimer usage in defining the role T-cell subsets play in T1D etiology and the therapeutic potential of pMHC for antigen-specific identification and modulation of diabetogenic T cells.

scholarly journals THE MAJOR HISTOCOMPATIBILITY COMPLEX: A REVIEW

2017 ◽  
Vol 10 (2) ◽  
pp. 33
Author(s):  
Preeti Sharma ◽  
Pradeep Kumar ◽  
Rachna Sharma
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
B Lymphocytes ◽  
T Lymphocyte ◽  
Antigen Processing ◽  
Major Histocompatibility ◽  
Peptide Fragments ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Stimulation Of

One of the important components of the immune system, the major histocompatibility complex (MHC) molecules allow T-lymphocytes to detect cells, such as macrophages, B-lymphocytes, and dendritic cells that ingest infectious microorganisms or the self-cells infected with microorganism. On being engulfed a microorganism, macrophage partially digests it and displays peptide fragments of the microbe on its surface, bound to MHC molecules and the T-lymphocyte recognizes the foreign fragment attached to the MHC molecule and binds to it, lead to stimulation of an immune response. The MHC molecule presents peptides from its own cell (self-peptides) in healthy self-cells to which T-cells do not normally react.Keywords: MHC, B Cells, T Cells, Antigen Processing. 

scholarly journals Antigen Presentation by Dendritic Cells after Immunization with DNA Encoding a Major Histocompatibility Complex Class II–restricted Viral Epitope

1997 ◽  
Vol 186 (9) ◽  
pp. 1481-1486 ◽  
Author(s):  
Sofia Casares ◽  
Kayo Inaba ◽  
Teodor-Doru Brumeanu ◽  
Ralph M. Steinman ◽  
Constantin A. Bona
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Antigen Presentation ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Dna Encoding ◽  
Histocompatibility Complex

Intramuscular and intracutaneous immunization with naked DNA can vaccinate animals to the encoded proteins, but the underlying mechanisms of antigen presentation are unclear. We used DNA that encodes an A/PR/8/34 influenza peptide for CD4 T cells and that elicits protective antiviral immunity. DNA-transfected, cultured muscle cells released the influenza polypeptide, which then could be presented on the major histocompatibility complex class II molecules of dendritic cells. When DNA was injected into muscles or skin, and antigen-presenting cells were isolated from either the draining lymph nodes or the skin, dendritic, but not B, cells presented antigen to T cells and carried plasmid DNA. We suggest that the uptake of DNA and/or the protein expressed by dendritic cells triggers immune responses to DNA vaccines.

scholarly journals Frequency analysis of cytotoxic T lymphocyte precursors in chimeric mice. Evidence for intrathymic maturation of clonally distinct self-major histocompatibility complex- and allo-major histocompatiblilty complex-restricted virus-specific T cells.

1981 ◽  
Vol 153 (6) ◽  
pp. 1517-1532 ◽  
Author(s):  
H Wagner ◽  
C Hardt ◽  
R Bartlett ◽  
H Stockinger ◽  
M Röllinghoff ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Lymphocyte ◽  
Sendai Virus ◽  
Cytotoxic T Lymphocyte ◽  
Major Histocompatibility ◽  
Chimeric Mice ◽  
Histocompatibility Complex

To study whether the thymic major histocompatibility complex (MHC) imposes a constraint on the receptor repertoire of maturating cytotoxic T lymphocyte (CTL) precursors, the restriction phenotypes of virus-specific CTL of MHC-compatible and of MHC-incompatible thymus- and bone marrow-grafted (A X B)F1 chimeric mice were compared. Dependent on the mode of in vitro sensitization, thymocytes or splenocytes of both types of chimeric mice generated Sendai virus-specific, self-MHC-or allo-MHC-restricted CTL. By applying the limiting-dilution technique, the CTL-precursor (CTL-P) frequencies of self-MHC-restricted and allo-MHC-restricted virus-specific T cells as well as of alloreactive T cells were determined. The data obtained revealed that independent of MHC differences between thymus and bone marrow, the frequencies of self-MHC-restricted and allo-MHC-restricted CTL-P were comparable, and in the same older of magnitude as those previously determined in conventionally reared mice. Self-MHC-restricted, virus-specific CTL-P were in a three- to fivefold excess over allo-MHC-restricted CTL-P. A segregation analysis revealed that clonally distinct CTL-P give rise to either self-restricted or allo-MHC-restricted, virus-specific CTL. Both sets were found not only in the spleen, but also in the thymus of chimeric mice, formally demonstrating the intrathymic differentiation pathway of self-MHC as well of allo-MHC-restricted CTL-P. These data reveal no major constraint of the thymic MHC on the capacity of T cells to recognize viral antigens either in the context of self-MHC or of allogeneic MHC products.

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