Contrasting contributions of complementarity-determining region 2 and hypervariable region 4 of rat BV8S2⁺ (V_β8.2) TCR to the recognition of myelin basic protein and different types of bacterial superantigens

In experimental autoimmune encephalomyelitis (EAE) of LEW rats, BV8S2⁺ (V_β8.2) T cells dominate the RT1B^l-restricted response to guinea pig myelin basic protein (gpMBP), and respond to the superantigens (SAg) Staphylococcus enterotoxin C1 (SEC1), Mycoplasma arthritidis SAg (MAS) and Yersinia pseudotuberculosis mitogen (YPM). T cells expressing the closely related BV8S4 differ from BV8S2 T cells in their response to gpMBP, and the SAg SEC1 and MAS, but not in their response to YPM. The functional differences between BV8S2 and BV8S4, which vary in complementarity-determining/hypervariable region 4 (CDR4/HV4) and CDR2, were analyzed by cloning and mutating a TCR with features typical for gpMBP-specific BV8S2⁺ TCR. The wild-type BV8S2 receptor and the BV8S4-like CDR2 + 4β double mutant of BV8S2 showed the same differences in ligand specificity as polyclonal BV8S2⁺ and BV8S4⁺ lymphocyte populations. The CDR2β mutant lost its reactivity for SEC1 and gpMBP_68–88, but the CDR4/HV4β mutation abolished only activation by SEC1. Thus, CDR2 and HV4 contribute not only differently to recognition of peptide antigens, but also to recognition of different types of bacterial SAg.