HLA and immune response
The most important function of HLA molecule is in the induction and regulation of immune responses. T cell recognize foreign antigen in combination with HLA molecules. In an immune response, foreign antigen is processed by and presented on the surface of a cell (eg. macrophage). The HLA molecule has a section, called its antigen (or peptide) – binding cleft, in which it has these antigens inserted. T cells interact with the foreign antigen/HLA complex and are activated. The T cell receptor usually reacts with foreign antigens in the form of peptides from the foreign material bound to HLA. The foreign peptide fills the groove of HLA, and the T cell receptor lies above the two in an approximately diagonal orientation. This allows the loops at the ends of the T cell receptor α and T cell receptor β strands to contact both HLA and foreign peptide, with the Complementary Determining Region (CDR1 and CDR2) sequences (which are encoded in the germ-line DNA for Vα and Vβ, respectively) contacting mostly the alpha helices of the HLA proteins themselves. However, the CDR3 regions of T cell receptor α and β (which are encoded by the random, non-germ-line sequences that are created by gene rearrangement) make many contacts with the foreign peptide.