Encephalitogenic, myelin basic protein-specific T cells from naive rat thymus: preferential use of the T cell receptor gene V beta 8.2 and expression of the CD4-CD8- phenotype.
Using a primary limiting dilution approach to generate T cell lines, we compared myelin basic protein (MBP)-specific T cell clones from naive unprimed Lewis rat thymuses with the corresponding T cell repertoire of primed rats. We found that in the native thymus repertoire MBP-specific, encephalitogenic T cell clones preferentially use T cell receptor V beta 8.2 genes, along with CDR3 sequences typical for the primed Lewis anti-MBP response. In contrast to T cells from primed immune organs, which all display the CD4+CD8- phenotype, the majority of naive thymus-derived T cell clones expressed reduced levels of the CD4 co-receptor. Some clones were completely CD4-CD8-, while others included CD4-CD8- subpopulations along with CD4+CD8- T cells. In the one mixed population examined in detail, the CD4-CD8- and CD4+CD8-T cell subpopulations used a T cell receptor with identical beta chain sequence. The data suggest that in the Lewis rat the biased T cell receptor gene usage by encephalitogenic T cells is a property of the natural thymic T cell repertoire, possibly as a consequence of positive selection. The unusually low expression of CD4 in the major histocompatibility complex class II-restricted autoreactive T cells could be related to their escape from negative selection within the thymus.
Lannes-Viera
J
J
Max-Planck-Institute of Psychiatry, Martinsried, Germany.
Goudable
B
B
Drexler
K
K
Gehrmann
J
J
Torres-Nagel
N
N
Hünig
T
T
Wekerle
H
H
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D005260:Female; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta