The Tritope Model for restrictive recognition of antigen by T-cells I. What assumptions about structure are needed to explain function?

被引:22
作者
Cohn, M [1 ]
机构
[1] Salk Inst Biol Studies, Conceptual Immunol Grp, La Jolla, CA 92037 USA
关键词
TCR; restrictive recognition; signaling mechanism; alloreactivity; positive and negative selection; repertoire;
D O I
10.1016/j.molimm.2005.01.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Given that the recognition of the allele-specific determinants expressed by MHC-encoded restricting elements (R) is germline encoded and selected, whereas the recognition of peptide (P) is somatically encoded and selected, then two different combining sites must be under selection. This necessitates a multirecognitive-single T-cell antigen-receptor (TCR) with anti-R and anti-P paratopes that function in concert to signal restrictive reactivity. The consequences of this "two repertoire" postulate not only gives us a concept of TCR structure quite distinct from that at present generally accepted, but, in addition, resolves many existent contradictions. The problems of the positive and negative selection, alloreactivity, Self-Nonself (S-NS) discrimination, the nature and size of the repertoire, and the related experimental interpretations, are discussed. Further the Tritope Model is compared with previously proposed models to justify why a competing model is warranted. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1419 / 1443
页数:25
相关论文
共 66 条
[21]   Quantitation of the cell surface level of L-d resulting in positive versus negative selection of the 2C transgenic T cell receptor in vivo [J].
Cook, JR ;
Wormstall, EM ;
Hornell, T ;
Russell, J ;
Connolly, JM ;
Hansen, TH .
IMMUNITY, 1997, 7 (02) :233-241
[22]   Recognition of a specific self-peptide: Self-MHC class II complex is critical for positive selection of thymocytes expressing the D10 TCR [J].
Dao, T ;
Blander, JM ;
Sant'Angelo, DB .
JOURNAL OF IMMUNOLOGY, 2003, 170 (01) :48-54
[23]   Ligand recognition by αβ T cell receptors [J].
Davis, MM ;
Boniface, JJ ;
Reich, Z ;
Lyons, D ;
Hampl, J ;
Arden, B ;
Chien, YH .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :523-+
[24]   T-CELL ANTIGEN RECEPTOR GENES AND T-CELL RECOGNITION [J].
DAVIS, MM ;
BJORKMAN, PJ .
NATURE, 1988, 334 (6181) :395-402
[25]  
DILLON SR, 1994, J IMMUNOL, V152, P1790
[26]   Immunology - Costimulation: Building an immunological synapse [J].
Dustin, ML ;
Shaw, AS .
SCIENCE, 1999, 283 (5402) :649-650
[27]  
Garcia K C, 1999, Rev Immunogenet, V1, P75
[28]   Structural basis of T cell recognition [J].
Garcia, KC ;
Teyton, L ;
Wilson, LA .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :369-+
[29]   EFFICIENT IMMUNE-RESPONSES IN MICE LACKING N-REGION DIVERSITY [J].
GILFILLAN, S ;
BACHMANN, M ;
TREMBLEAU, S ;
ADORINI, L ;
KALINKE, U ;
ZINKERNAGEL, R ;
BENOIST, C ;
MATHIS, D .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (11) :3115-3122
[30]   DO ANTIGENIC PEPTIDES HAVE A UNIQUE SENSE OF DIRECTION INSIDE THE MHC BINDING GROOVE - A MOLECULAR MODELING STUDY [J].
GOPALAKRISHNAN, B ;
ROQUES, BP .
FEBS LETTERS, 1992, 303 (2-3) :224-228