T cell receptors for responses to Mls determinants and allo-H-2 determinants appear to be encoded on different chromosomes.

Abstract

Previous studies have shown that T cell clones specific for strong Mlsa,d determinants concomitantly display apparently random reactivity to allo-H-2 determinants. One explanation for this finding is that T cell recognition of Mlsa,d and allo-H-2 determinants is controlled by separate sets of receptors. If these receptors were chromosomally unlinked, karyotypically unstable T cell hybrids with dual reactivity for Mlsa,d and particular allo-H-2 determinants would be expected, occasionally, to lose reactivity for one set of determinants, but not the other. The results presented here provide direct support for this prediction.

Properties of the Mls System: A Revised Formulation of Mls Genetics and an Analysis of T‐Cell recognition of Mls Determinants

“…The results of this analysis are given in Table II. All four of the clones derived from two independent BIO.BR anti-AKR/J lines responded to CBA/J stimulators as well as to the original AKR/J stimulators, a pattern which has been reported by several investigators (Webb et al 1981, Jones & Janeway 1982, Lynch et al 1985. Among BIO.BR anti-C3H/HeJ clones which were also derived from two independent T-cell lines, four clones were found to be autoreactive and to be specific for self Aa'^A/f' or Ea'^E^ determinants.…”

“…More intriguing and more speculative is the possibility that Mis products might also function in positive selection during T-cell development, as proposed by Kappler et al (1988). In addition to this evidence supporting a role for the ap TCR in Mis recognition, arguments have been presented by Webb et al for the essential role of a second, distinct receptor for Mis (Webb et al 1985(Webb et al , 1988. It is possible, for example, that the interaction between Mis' and an MIs'=-specific receptor would increase the overall T cell-stimulator cell interaction mediated by affinity of the TCR Vŝ egment for a class II epitope.…”

“…Although this pattern of Mis-stimulatory ability has been observed by several laboratories (Festenstein 1973, Janeway et al 1976, Abe et al 1987b, Click et al 1987), some investigators have described different patterns. For example, the weak stimulatory ability of Mis' has not been detected in some studies (Molnar-Kimber & Sprent 1981), and Mis" and Mis" have been reported to be highly crossreactive and even antigenically indistinguishable in certain conditions (Webb et al 1981). These results led some investigators to propose that the Mis locus has only two alleles, the "a/d" allele encoding nonpoly-morphic determinants which cause strong MLR, and the non stimulatory or null "b" allele .…”

“…Therefore, some investigators have suggested that the Mis genes do not encode structural cell surface alloantigens recognized by the TCR a/? dimer, and that the Mis-specific response of T cells may be mediated by non-specific lectin-like interactions of Mis gene products expressed on antigen-presenting cells with complementary T-cell structures (Webb et al 1981(Webb et al , 1985. In order to address questions of the mechanism of T-cell recognition of Mis gene products, and furthermore to examine the potential role of Mis products in T-cell repertoire formation, the relationship between Mis reactivity and T-cell recognition of conventional foreign antigens was examined (Abe et al 1988d).…”

Downregulation of T cell responses by antibodies to the T cell receptor.

“…Although it is generally accepted that reactivity to self + X and allo-H-2 determinants reflects crossreactive recognition by a single set of TcR a-,8 heterodimers (1, 8), we have previously reported data suggesting that Mls determinants might be recognized by a different cell surface molecule (9). The strongest evidence against this notion has been the demonstration that Mls-reactivity can be inhibited by typical anti-TcR mAb (1,(4)(5)(6).…”