62 Analysis of T Cell Alloreactivity

The genetic and biochemical basis for the inclusion of T cell alloreactivity within the immunological repertoire of T helper (Tn) 1 lymphocytes remains a perplexing problem (1, 2). Recent evidence (3-9) suggests that the ability of Tn cells to bind to molecular complexes formed on antigen-presenting ceils between a nominal antigen and either self or nonself (allo) Ia molecules regulates their different phenotypic patterns of immune responsiveness. This type of regulation implies that antigen presentation markedly influences the TH cell repertoire (t0). It is likely that this repertoire is governed by the diversity and specificity of Tn cell membrane receptors for epitopes of the nominal antigen and either selfor allo-Ia molecules. Because selfand allo-Ia molecules express not only private epitopes but also public epitopes (1113), it is conceivable that their TH cell-derived self-Ia and allo-Ia complementa ry receptors possess some structural similarities (reviewed in 1, 14). This proposed structural homology of different Ia receptors might enable a self-Ia receptor to bind with high affinity to a self-Ia molecule and with lower affinity to an allo-Ia molecule; the reverse is expected for an allo-Ia receptor. It is apparent , therefore, that a better unders tanding of the biological relationship between T cell self-reactivity and alloreactivity should emerge from a study of the binding capaci ty of alloactivated T cells for self-Ia and allo-Ia molecules. Using immunofluorescence, we have previously shown (15, 16) that dur ing a graft vs. host reaction (GVHR), Lytl+2 donor T cell blasts bind detectable amounts o f allo-Ia molecules of host origin but not self-Ia molecules of donor origin. Host-derived