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 surface. In general, class I and class II MHC products provide a context for the recognition of foreign antigens by CD8+ and CD4+ T cells, respectively. This recognition seems to be largely dependent on alpha beta TCR heterodimers, whereas the function of the second gamma delta TCR, present on a minor subpopulation of cells, is still unknown. 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 evidence. 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 antigens. The function of the relatively invariant Qa and Tla molecules remains unknown. 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 gamma delta 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.

Diversity of γδ T-cell antigens

“…Most prominently, a response of a cd hybridoma to poly GT, a polymer of approximately 100 amino acids containing glutamic acid and tyrosine at a 1 : 1 ratio, was published as early as 1989. 97 We later showed that essentially all Vc1 1 cd T cells respond to poly GT, 18 as well as cells expressing other cd TCRs, but we were unable to confirm the original claim that poly GT is recognized in the context of Qa-1 b . With its random sequence, poly GT is not a defined Ag and does not have a defined structure.…”

MHC class I-dependent Vγ4+pulmonary T cells regulate αβ T cell-independent airway responsiveness

“…The increase required ␤ 2 M and TAP-1 expression, implying that the affected V␥4 ϩ T cells respond to MHC class I or related molecules. With the possible exception of Qa-1 b -reactive cells (30), all MHC class I-specific murine ␥␦ T cells characterized thus far express V␥4 (31)(32)(33)(34). This survey suggests that the V␥4 ϩ T cell subset is biased toward MHC class I recognition.…”

A Peptide from Heat Shock Protein 60 Is the Dominant Peptide Bound To Qa-1 in the Absence of the MHC Class Ia Leader Sequence Peptide Qdm

“…Anti-Qa-1 Abs have been shown to block recognition of the copolymer Glu 50 -Tyr 50 by a ␥␦ T cell hybridoma (27). Tompkins et al (28) demonstrated that Qa-1 b -restricted T cell hydribomas generated by immunizing low-responder H-2 b mice with pork insulin recognize an insulin B chain determinant in a TAP-independent fashion.…”