Qa-1 restricted recognition of foreign antigen by a γδ T-cell hybridoma

Abstract

DISTINCT T-lymphocyte subsets recognize antigens in conjunction with different classes of major histocompatibility complex (MHC) glycoproteins using the T-cell receptor (TCR), a disulphide-linked heterodimer associated with the CD3 complex on the cell surface¹. In general, class I and class II MHC products provide a context for the recognition of foreign antigens by CD8⁺ and CD4⁺ T cells, respectively². This recognition seems to be largely dependent on αβ TCR heterodimers^3,4, whereas the function of the second γδ TCR, present on a minor subpopulation of cells, is still unknown⁵. In the mouse, the existence of six cell-surface MHC class I products (K, D, L, Qa-1, Qa-2 and Tla) has been firmly established by serological, biochemical and genetic evidence⁶. So far, only the most polymorphic of them, K, D and L ('classical' class I) have been reported as restriction elements for T-cell recognition of foreign antigens¹. The function of the relatively invariant Qa and Tla molecules remains unknown^6,7. We have made a T-helper cell hybridoma clone (DGT3) that recognizes synthetic copolymer poly(Glu⁵⁰Tyr⁵⁰) in the context of Qa-1 cell surface product, and has a CD4⁻CD8⁻ phenotype. Our studies indicate that DGT3 cells express the γδ TCR on the cell surface, implicating its role in Qa-1-restricted antigen recognition. This is the first evidence that T cells can recognize foreign antigen in association with self Qa product, confirming that Qa molecules not only topologically, but also functionally, belong to the MHC.