The Role of H-2-Linked Genes in Helper T Cell Function

Abstract

Abstract We have studied the H-2 genes that control interactions between antigen-presenting macrophages (Mø) and helper T cells both during and after priming. B6AF1 (H-2b × H-2a) mice were initially primed in vivo with keyhole limpet hemocyanin (KLH)-pulsed Mø of either parental H-2 type, and their T cells were tested for helper activity in the in vitro anti-trinitrophenol (TNP) response to TNP-KLH. In each case, F1 T cells cooperated well only with B cells and Mø having the same K-I-A subregion as the Mø used for priming. In a second approach, F1 mice were instead primed with free antigen, and T cells enriched in specific helper function were then isolated in vitro by adherence to antigen-pulsed parental Mø. The F1 T cells isolated in this manner exhibited enriched helper activity only when tested with B cells and Mø that had the K-I-A region type of the Mø used for isolation. With this technique, the same genetic restrictions were also found for responses to sheep red blood cells (SRBC). A direct role for I-region genes in this system was established by the ability of anti-Ia alloantisera to specifically inhibit the enrichment of helper T cells on Mø monolayers. Taken together these results pinpoint I-A as the relevant subregion involved in the associative recognition of these complex antigens by helper T cells.