T cell idiotypes recognizing self‐major histocompatibility complex molecules: H‐2 specificity, allotype linkage, and expression on functional T cell populations

Abstract

An anti-idiotypic serum (antiserum 5936, B. Rubin et al., J. Exp. Med. 1979. 150: 307) was used to demonstrate receptor sites for self-major histocompatibility complex (MHC) antigens on T lymphocytes. The antiserum was raised by injecting rabbits tolerant to mouse Ig with a B6 anti-CBA (anti-H2k) alloantibody. It recognized a large proportion of T cells from H-2k strains carrying the b, c, d or e allele at the Igh-1 locus, but only a few T cells from H-2k strains with Igh-1 alleles a, f and j. Allotype linkage of the 5936 idiotype was also demonstrated by segregation analysis. The antiserum did not recognize either H-2k B cells or T cells from other H-2 haplotypes despite the presence of a permissive Igh-1 allele. The 5936 idiotype was found to be associated with several different antigen specificities, indicating that it is not located on the binding site for foreign antigen. Furthermore, the 5936 antiserum inhibited the binding of soluble Ik antigens by H-2k, Igh-1b, T cells, and, in the presence of complement, eliminated T cells responding to different antigens in an I-Ak-restricted fashion. Collectively, the data indicate that the structure bearing the 5936 idiotype is a receptor for I-Ak antigens, expressed by strains carrying the I-Ak allele and a permissive allele at the Igh-1 locus. The relevance of this finding to the MHC-restricted recognition of antigens by T cells is discussed.

The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody.

“…Most efforts have focused on T cells or T cell products that have been demonstrated to bind free antigen (Ag), because in these cases an easily definable function could be used to assay any likely candidates that were identified. Using material of this kind, it has been suggested that T cell Ag receptors bear determinants that are cross-reactive with antibody idiotypes or VH (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and which also map to the major histocompatibility complex (MHC) t (7,(13)(14)(15)(16)). In addition, antisera raised against surface proteins on' T cells, especially suppressor T cells, have suggested that determinants mapping near Igh are displayed on the surfaces of some types of T cells and are intimately involved with Ag recognition by these cells (17)(18)(19).…”

Use of somatic cell genetics to study chromosomes contributing to antigen plus I recognition by T cell hybridomas.

“…Hybridomas Derived from Fusions to Rb (16,17)7 T Cell Blasts. Five Rb(16.17)7 mice were primed with KLH; 7 d later, cells from draining lymph nodes were cultured with KLH followed by IL-2, and fused to FS6-14.13.AG2.1 as described in Materials and Methods.…”

“…Discussion Considerable interest centers on mapping genes that code T cell receptor(s) for Ag/ L In fact finding the chromosomes that do not bear the receptor(s) is probably as significant as finding the ones that do, depending on which these turn out to be. Various theoretical and experimental considerations have suggested that in the mouse genes controlling Ag/I receptors should be found on chromosomes bearing immunoglobulin heavy chain genes and/or MHC genes, i.e., chromosomes 12 and 17, respectively (6)(7)(8)(9)(10)(11)(12)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Since on occasion Ag-binding T cell products have been shown to bear immunoglobulin idiotypes thought to be controlled by a combination of immunoglobulin light and heavy chains, chromosomes bearing light chain genes, i.e., chromosomes 6 and 16 (21,22), may also be implicated, although this is apparently not necessarily true (35).…”

Biochemistry and Distribution of the T Cell Receptor

“…Likewise Ag may sometimes have a detectable affinity for certain MHC products. Examples of such affinities have been reported (Nagy et al 1982 , Rock & Benacerraf 1983a, b, Rao et al 1984, Werdelin 1982) but we do not believe they imply that such affinities can always be measured because certainly this is not usually the case (Zeigler & Unanue 1979, Marrack et al 1983c, Shimonkevitz et al 1984. Moreover the requirement for the virgin T cell to recognize cell-bound antigen in order to receive accessory signals such as IL-1 (Unanue & Kiely 1977, Farrar et al 1980 or to function effectively (Sprent 1978) might preclude the T cell having too high an affinity for free Ag.…”