The Antigen-Specific, Major Histocompatibility Complex-Restricted Receptor on T Cells

We have examined the role of the murine homologue of Leu-3 T4, L3T4, in recognition of antigen in association with products of the major histocompatibility complex (Ag/MHC) by murine T cell hybridomas. A series of ovalbumin (OVA)/I-Ad-specific T cell hybridomas were ranked in their sensitivity to Ag/I by measuring their ability to respond to low doses of OVA, or their sensitivity to inhibition by anti-I-Ad antibodies. T cell hybridomas with low apparent avidity for OVA/I-Ad, i.e. that did not respond well to low concentrations of OVA and were easily inhibited by anti-I-Ad, were also easily inhibited by anti-L3T4 antibodies. The reverse was true for T cell hybridomas with apparent high avidity for Ag/MHC. We found that the presence of low doses of anti-L3T4 antibodies caused T cell hybridomas to respond less well to low doses of Ag, and to be more easily inhibited by anti-I-Ad antibodies. These results suggested that the role of the L3T4 molecule is to increase the overall avidity of the reaction between T cells and Ag-presenting cells. In support of this idea was the discovery of several L3T4- subclones of one of our L3T4+ T cell hybridomas, D0.11.10. The L3T4- subclones had the same amount of receptor for OVA/I-Ad as their L3T4+ parent, as detected by an anti-receptor monoclonal antibody. The L3T4- subclones, however, responded less well to low doses of OVA, and were more easily inhibited by anti-I-Ad antibodies than their L3T4/ parent. These results showed that the L3T4 molecule was not required for surface expression of, or functional activity of, the T cell receptor for Ag/MHC. The L3T4 molecule did, however, increase the sensitivity with which the T cell reacted with Ag/MHC on Ag-presenting cells.

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The Role of Peptides in T Cell Alloreactivity Is Determined by Self–Major Histocompatibility Complex Molecules

Journal of Experimental Medicine ◽

10.1084/jem.191.5.805 ◽

2000 ◽

Vol 191 (5) ◽

pp. 805-812 ◽

Cited By ~ 62

Author(s):

Reinhard Obst ◽

Nikolai Netuschil ◽

Karsten Klopfer ◽

Stefan Stevanović ◽

Hans-Georg Rammensee

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

Target Cells ◽

Major Histocompatibility ◽

Complex Molecules ◽

Mhc Molecules ◽

Histocompatibility Complex ◽

Alloreactive T Cells

By analyzing T cell responses against foreign major histocompatibility complex (MHC) molecules loaded with peptide libraries and defined self- and viral peptides, we demonstrate a profound influence of self-MHC molecules on the repertoire of alloreactive T cells: the closer the foreign MHC molecule is related to the T cell's MHC, the higher is the proportion of peptide-specific, alloreactive (“allorestricted”) T cells versus T cells recognizing the foreign MHC molecule without regard to the peptide in the groove. Thus, the peptide repertoire of alloreactive T cells must be influenced by self-MHC molecules during positive or negative thymic selection or peripheral survival, much like the repertoire of the self-restricted T cells. In consequence, allorestricted, peptide-specific T cells (that are of interest for clinical applications) are easier to obtain if T cells and target cells express related MHC molecules.

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Major histocompatibility complex-restricted recognition of retroviral superantigens by V beta 17+ T cells.

Journal of Experimental Medicine ◽

10.1084/jem.176.1.275 ◽

1992 ◽

Vol 176 (1) ◽

pp. 275-280 ◽

Cited By ~ 15

Author(s):

M A Blackman ◽

F E Lund ◽

S Surman ◽

R B Corley ◽

D L Woodland

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

Mhc Class Ii ◽

Class Ii ◽

Major Histocompatibility ◽

Direct Role ◽

Histocompatibility Complex ◽

Class Ii Mhc ◽

Mhc Class Ii Molecules

It has been established that at least some V beta 17+ T cells interact with an endogenous superantigen encoded by the murine retrovirus, Mtv-9. To analyze the role of major histocompatibility complex (MHC) class II molecules in presenting the Mtv-9 encoded superantigen, vSAG-9 to V beta 17+ hybridomas, a panel of nine hybridomas was tested for their ability to respond to A20/2J (H-2d) and LBK (H-2a) cells which had been transfected with the vSAG-9 gene. Whereas some of the hybridomas recognized vSAG-9 exclusively in the context of H-2a, other hybridomas recognized vSAG-9 exclusively in the context of H-2d or in the context of both H-2d and H-2a. These results suggest that: (a) the class II MHC molecule plays a direct role in the recognition of retroviral superantigen by T cells, rather than serving simply as a platform for presentation; and, (b) it is likely that components of the TCR other than V beta are involved in the vSAG-9/TCR/class II interaction.

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Studies on the generation of human erythroid burst promoting activity from alloreactive T cells clones: Role of major histocompatibility complex determinants

Human Immunology ◽

10.1016/0198-8859(85)90083-7 ◽

1985 ◽

Vol 14 (2) ◽

pp. 112

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Alloreactive T Cells

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The Interaction of Antigens and Superantigens with the Human Class II Major Histocompatibility Complex Molecule HLA-DR1

Biological NMR Spectroscopy ◽

10.1093/oso/9780195094688.003.0022 ◽

1997 ◽

Author(s):

T. Jardetzky

Keyword(s):

Immune Response ◽

T Cells ◽

Major Histocompatibility Complex ◽

Immune System ◽

Complex Molecule ◽

Thymic Selection ◽

Major Histocompatibility ◽

Peptide Antigens ◽

Histocompatibility Complex ◽

Unique Specificity

The initiation and maintenance of an immune response to pathogens requires the interactions of cells and proteins that together are able to distinguish appropriate non-self targets from the myriadof self-proteins (Janeway and Bottomly, 1994). This discrimination between self and non-self is in part accomplished by three groups of proteins of the immune system that have direct and specific interactions with antigens: antibodies, T cell receptors (TcR) and major histocompatibility complex (MHC) proteins. Antibodies and TcR molecules are clonally expressed by the B and T cells of the immune system, respectively, defining each progenitor cell with a unique specificity for antigen. In these cell types both antibodies and TcR proteins undergo similar recombination events to generate a variable antigen combining site and thus produce a nearly unlimited number of proteins of different specificities. TcR molecules are further selected to recognize antigenic peptides bound to MHC proteins, during a process known as thymic selection, restricting the repertoire of T cells to the recognition of antigens presented by cells that express MHC proteins at their surface. Thymic selection of TcR and the subsequent restricted recognition of peptide-MHC complexes by peripheral T cells provides a fundamental molecular basis for the discrimination of self from non-sell and the regulation of the immune response (Allen, 1994; Nossal, 1994; von Boehmer, 1994). For example, different classes of T cells are used to recognize and kill infected cells (cytotoxic T cells) arid to provide lymphokiries that induce the niajority of soluble antibody responses of B cells (helper T cells). In contrast to the vast combinatorial and clonal diversity of antibodies and TcRs, a small set of MHC molecules is used to recognize a potentially unlimited universe of foreign peptide antigens for antigen presentation to T cells (Germain, 1994). This poses the problem of how each MHC molecule is capable of recognizing enough peptides to insure an immune response to pathogens. In addition, the specificity of the TcR interaction with MHC-peptide complexes is clearly crucial to the problem of self :non-self discrimination, with implications for both protective immunity and auto-immune disease.

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