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.
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.
Kreiss
Matthias
M
Institute for Virology and Immunobiology, University of Würzburg, Würzburg 97078, Germany.
Asmuss
Anne
A
Krejci
Kathrin
K
Lindemann
Dirk
D
Miyoshi-Akiyama
Tohru
T
Uchiyama
Takehiko
T
Rink
Lothar
L
Broeren
Chris P M
CP
Herrmann
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D003001:Cloning, Molecular; D022801:Complementarity Determining Regions / Q000235:genetics* / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008934:Mitogens / Q000276:immunology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology*; D011506:Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015704:CD4 Antigens; D022801:Complementarity Determining Regions; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D006649:Histocompatibility Antigens; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C109168:T-cell receptor Vbeta 8.2; C093313:Yersinia pseudotuberculosis-derived mitogen; C038353:histocompatibility antigens RT, rat; C079716:myelin basic protein 68-88; C034959:enterotoxin C, staphylococcal