Characterization of the response to myelin basic protein in a non human primate model for multiple sclerosis.
The common marmoset Callithrix jacchus (C. jacchus) is an outbred species characterized by a naturally occurring bone marrow chimerism and susceptibility to a form of experimental autoimmune encephalomyelitis (EAE) resembling multiple sclerosis (MS). T cell clones specific for the myelin antigen, myelin basic protein (MBP), can be derived from both naive and immunized marmosets and can adoptively transfer EAE to compatible chimeric siblings. Here, we demonstrate that several different antigenic determinants of MBP are recognized by these encephalitogenic T cell clones. Furthermore, PCR-based analysis of TCR Vbeta families does not show the preferential usage of any gene segment. Characterization of third complementarity determining regions (CDR3) fails to demonstrate a recurring motif characteristic of the T cell immune response to MBP in this species. Nevertheless, brief amino acid motifs are shared among marmoset clones and CDR3 sequences from MS samples. These data suggest that, due to its outbred condition, the C. jacchus marmoset mounts a diverse pathogenic response to MBP. However, the findings that certain CDR3 sequences are identically expressed in different animals, or by different T cell clones, suggest that MBP-specific T cell populations may be clonally expanded following chronic antigenic stimulation in vivo.
Uccelli
A
A
Department of Neurological Sciences and Vision, Gaslini Institute, University of Genoa, Italy. auccelli@neurologia.unige.it
Giunti
D
D
Mancardi
G
G
Caroli
F
F
Fiorone
M
M
Seri
M
M
Hauser
S L
SL
Genain
C P
CP
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002144:Callithrix; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta