Cytotoxic T-cell responses show more restricted specificity for self than for non-self H-2D-coded antigens

Abstract

The specificity of recognition of H-2 antigens by various subsets of Tc cells was investigated with respect to the two separate molecules known to be coded in the H-2D(d) region (a) D which carries the private specificity H-2.4 and (b) D' which carries the public specificity H-2.28. BALB/c.H-2(db) mutant mice express D but not D' on their cell surfaces, whereas wild-type BALB/c mice express both D and D'. H-2 restricted Tc cells specific for viral-plus- H-2D(d)-coded antigens on infected self cells, or minor H-plus-H-2D(d)-coded antigens on H-2-compatible cells apparently recognize D, but do not detectably recognize D. In contrast, BALB/c-H-2(db) anti-BALB/c Tc cell responses do recognize D' (the only known antigen which is not shared by mutant and wild-type); furthermore, D' is also detectably recognized by a significant proportion of the Tc cells that respond in MLR to H-2D(d)-coded antigens. In these latter responses, D' was recognized separately from D, i.e., the response was not "H-2 restricted". These results indicate that H-2 restricted Tc cell responses to modified-self cells are more specific for self H-2D(d)-coded antigens then are allogeneic Tc cell responses directed at the same antigens, in that haplotype-unique (private) specificity recognition (of the D molecule) exclusively occurs only in the former, not the latter case. The implications of this specificity of H-2 restricted responses for possible processes of somatic selection of anti-self recognition structures on progenitor Tc cells are briefly discussed.

Involvement of H-2L gene products in virus-immune T-cell recognition. Evidence for an H-2L-restricted T-cell response.

“…Although influenza-immune T cells apparently recognize H-2L specificities, current studies using the same alloantisera and mouse strains indicate that there is no H-2Lrestricted component in the T-cell response to trinitrophenyl (TNP)-modified cells . 2 Blanden and Kees (24) recently reported that T cells generated against ectromelia virus and minor histocompatibility antigens do not recognize H-2L specificities . Thus, T cells appear to possess a more selective repertoire of responses associated with L than with K or D antigens.…”

The Complexity of Structures Involved in T-Cell Activation

“…This was shown by cold target inhibition experiments as well as inhibition studies with H-2Ld directed monoclonal antibodies. However, H-2L-restricted responses are not found against trinitrophenol (1 11) or minor histocompatibility antigens (22). We can discuss these results by employing the same conventions in describing the relationships between MHC class I molecules and nominal antigen as were used earlier in conjunction with la restriction elements (see p. 476).…”

TheH-2L locus and the system of H-2 specificities

“…The pattern of this cross-killing was in both cases similar to that of the H-2.28 family, but with greater quantitative variation. Thus, both Blanden and Kees (1978) and Melief (Kohn et al 1978) report that the highest killing is against BALB/c (and other D d) targets, the DBA/1 targets (H-2 q) are the second best. The cross-killing of 1t-2 q targets is due to D-region determinants, since BI0.AKM (K k D q) targets are killed, while H-2 k targets are not killed at all (Melief, personal communication).…”

“…The specificity of the CML reaction has been studied by Melief (see Kohn et al 1978) and by Blanden and Kees (1978). In both reports BALB/c-H-2 din2 lymphocytes sensitized against BALB/cKh cells were able to kill not only BALB/cKh target cells, but also target strains from several other H-2.28 positive strains.…”