Role of Ia Antigens in Clonal Deletion of T Cells: Studies with Recombinant and Transgenic Mice

Abstract

The Mls locus was discovered nearly 20 years ago by Hilliard Festenstein (1973). In the beginning it was merely a curiosity as to what other genes besides the major histocompatibility complex were involved in the mixed lymphocyte reactions. In the 1970’s, more laboratories started looking at this locus because incompatibility at the Mls locus activated much higher frequency of T cells than the MHC (Janeway and Katz, 1985). A major breakthrough came in the early 1980’s in the elucidation of the Mls locus when two laboratories showed that specific T cell receptors can be clonally deleted in the context of certain MHC class II molecules and Mls locus (Kappler, Staerz, White and Marrack 1988; MacDonald, Schneider, Lees, Howe, Acha-Orbea, Festenstein, Zinkernagel and Hengartner 1988). T cells bearing V_B6 and V_B8.1 T cell receptors were reactive to Mls and in Mls-l^a positive animals these T cells were clonally deleted. A hierarchy of response to Mls was found in H-2 haplotype both in vitro and in vivo.