Predominant use of a V_α gene segment in mouse T-cell receptors for cytochrome c

Abstract

The T-cell receptor is a cell surface heterodimer consisting of an α and a β chain that binds foreign antigen in the context of a cell surface molecule encoded by the major histocompatibility complex (MHC), thus restricting the T-cell response to the surface of antigen presenting cells^1–4. The variable (V) domain of the receptor binds antigen and MHC molecules and is composed of distinct regions encoded by separate gene elements—variable (V_α and V_β), diversity (D_β) and joining (J_α and J_β)—rearranged and joined during T-cell differentiation to generate contiguous V_α and V_β genes^5–11. T-helper cells, which facilitate T and B cell responses, bind antigen in the context of a class II MHC molecule. The helper T-cell response to cytochrome c in mice is a well-defined model for studying the T-cell response to restricted antigen and MHC determinants. Only mice expressing certain class II molecules can respond to this antigen (E^k_α E^k_β, E^k_α E^b_β, E^v_α E^v_β and E^k_α E^s_β)^12–14. Most T cells appear to recognize the C-terminal peptide of cytochrome c (residues 81–104 in pigeon cytochrome c)^15–18. We have raised helper T cells to pigeon cytochrome c or its C-terminal peptide analogues in four different MHC congenic strains of mice encoding each of the four responding class II molecules. We have isolated and sequenced seven V_α genes and six V_β genes and analysed seven additional helper T cells by Northern blot to compare the structure of the V_α and V_β gene segments with their antigen and MHC specificities. We have added five examples taken from the literature^19–22. These data show that a single V_α gene segment is responsible for a large part of the response of mice to cytochrome c but there is no simple correlation of MHC restriction with gene segment use.