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 [cytotoxic thymus-derived lymphocyte] cells was investigated with respect to the 2 separate molecules known to be coded in the H-2Dd region, D which carries the private specificity H-2.4 and 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 D and D''. H-2 restricted Tc cells specific for viral-plus-H-2Dd-coded antigens on infected self cells, or minor H-plus-H-2Dd-coded antigens on H-2-compatible cells apparently recognize D, but do not detectably recognize D''. In contrast, BALB/c-H-2db 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 [mixed lymphocyte reaction] to H-2Dd-coded antigens. In these latter responses, D'' was recognized separately from D, i.e., the response was not H-2 restricted. H-2 restricted Tc cell responses to modified-self cells are more specific for self H-2Dd-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 were briefly discussed.