CD4+ Class I-Restricted T Cells Specific for HIV gp160 315-329

Mature, circulating, αβ T cells express either CD4 or CD8. In the majority of cases, CD4+ T cells recognize Ag in association with class II MHC molecules, while CD8+ T cells recognize Ag in association with class I MHC molecules. In this report we describe CD4+ class I-restricted T cell hybridomas and normal clones specific for the peptide 315-329 of HIV gp160 strain IIIb in association with H-2Dd. Two models were formulated to explain how CD4+ class I-restricted T cells could arise. First, they could represent aberrant selection of CD4+ cells on class I MHC molecules in the thymus. Alternatively, they could have been selected normally on class II; in this case the cells would display cross-reactive recognition of 315-329 in association with H-2Dd and an unknown Ag in association with class II. To distinguish these models, a second specificity was determined for the T cell clones. The normal clones recognized the class I molecule H-2Kk as alloantigen and thus were presumably positively selected in the thymus on class I MHC. CD4 was shown to be functional in these cells in that anti-CD4 mAb inhibited their proliferation; however, both Ag- and Con A-induced responses were inhibited, suggesting that a negative signal was delivered by the anti-CD4 mAb.