Isolation and characterization of an I-A-restricted T cell clone with dual specificity for poly(Glu⁶⁰Ala³⁰Tyr¹⁰) (GAT) and Mls(a,d)

We have isolated a BALB/c (H-2(d), Mls^b) T cell clone (JTL-G12) specific for the synthetic polypeptide antigen poly(Glu⁶⁰Ala³⁰Tyr¹⁰) (GAT) in the context of self I-A determinants and for Mls(a,d) antigens in the absence of GAT. JTL-G12 proliferation in response to GAT was mapped to the K(d), I-A(d) subregions by using inbred H-2 congenic and recombinant strains. In addition, monoclonal antibody directed against I-A(d) but not K(d) or I-A(s) determinants blocked JTL-G12 proliferation in response to GAT presented by syngeneic splenocytes, indicating I-A restriction. The Mls cross-reactivity of this clone was verified by using a panel of inbred strains bearing the Mls(a,b,c,d) alleles and by using BXD recombinant inbred strains bearing the Mls^a allele or the Mls^b allele. All of the Mls^a BXD strains of the H-2(d) or H-2^b haplotypes stimulated JTL-G12 in the absence of GAT, whereas all of the Mls^b BXD strains were nonstimulatory. This response pattern is in complete accordance with recognition of the Mls^a determinant encoded by Mls or closely linked loci on chromosome 1. JTL-G12 proliferation in response to GAT/I-A(d) and Mls(a,d) determinants could be blocked with a monoclonal antibody (GK1.5) directed against L3T4, a structure involved in class II major histocompatibility complex antigen recognition. These results suggest that antigen/class II responsiveness, Mls reactivity, and expression of L3T4 can be properties of a single T cell population.