The molecular basis of alloreactivity in antigen-specific, major histocompatibility complex-restricted T cell clones

Abstract We have studied the relationship between major histocompatibility complex (MHC)-restricted antigen recognition and alloreactivity by examining T cell receptor (TCR) α and β gene expression in cytochrome c-specific, E k α :E k β (E k )-restricted helper T cell clones derived from B10.A mice. The clones could be segregated on the basis of four distinct alloreactivity patterns. Clones cross-reactive for three different allogeneic la molecules (A s α :A s β [A s ], A b α :A b β [A b ], E k α :E b β [E b ]) expressed the same Vα and Vβ gene segments, generating the distinct alloreactive specificities via unique Vα-Jα and Vβ-Dβ-Jβ joining events. E k α :E s β (E s )-alloreactive B10. A clones expressed the same Vα, Jα, and Vβ segments as an E s -restricted, E k -alloreactive, cytochrome c-specific, H-2-congenic B10.S(9R) clone. This homology between TCRs mediating allorecognition of la molecules and recognition of the same la molecules as restriction elements associated with nominal antigen suggests that MHC-restricted recognition and allorecognition represent differences in the affinity of the TCR-MHC molecule interaction.