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More MS news articles for June 2004

Contrasting contributions of complementarity-determining region 2 and hypervariable region 4 of rat BV8S2+ (Vbeta8.2) TCR to the recognition of myelin basic protein and different types of bacterial superantigens

Int Immunol. 2004 May;16(5):655-63. Epub 2004 Mar 29
Kreiss M, Asmuss A, Krejci K, Lindemann D, Miyoshi-Akiyama T, Uchiyama T, Rink L, Broeren CP, Herrmann T.
Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg 97078, Germany.

In experimental autoimmune encephalomyelitis (EAE) of LEW rats, BV8S2(+) (V(beta)8.2) 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 + 4beta double mutant of BV8S2 showed the same differences in ligand specificity as polyclonal BV8S2(+) and BV8S4(+) lymphocyte populations.

The CDR2beta mutant lost its reactivity for SEC1 and gpMBP(68-88), but the CDR4/HV4beta 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.