T cell response in @entity6503 ( XXXX ): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire.

@entity19 @entity6503 @entity13743 @entity792
T cells that can respond to self-antigens are present in the peripheral immune repertoire of all healthy individuals. Recently we have found that unmanipulated SJL @entity19 that are highly susceptible to @entity6503 also maintain a very high frequency of T cells responding to an encephalitogenic epitope of a myelin antigen proteolipid protein ( @entity13743 ) 139-151 in the peripheral repertoire. This is not due to lack of expression of myelin antigens in the thymus resulting in escape of @entity13743 139-151 reactive cells from central tolerance, but is due to expression of a splice variant of @entity13743 named @entity13743 , which lacks the residues 116-150. In spite of this high frequency, the @entity13743 139-151 reactive cells remain undifferentiated in the periphery and do not induce spontaneous @entity6503 . In contrast, SJL TCR @entity19 expressing a receptor derived from a pathogenic T cell clone do develop spontaneous disease. This may be because in normal @entity19 , autoreactive cells are kept in check by an alternate @entity13743 139-151 reactive nonpathogenic repertoire, which maintains a balance that keeps them healthy. If this is the case, selective activation of one repertoire or the other may alter susceptibility to @entity792 . Since T cells are generally cross-reactive, besides responding to nonself-antigens, they also maintain significant responses to self-antigens. Based on the @entity13743 139-151 system, we propose a model in which activation with foreign antigens can result in the generation of pathogenic memory T cells that mediate autoimmunity. We also outline circumstances under which activation of self-reactive T cells with foreign antigens can generate selective tolerance and thus generate protective/regulatory memory against self while still maintaining significant responses against foreign antigens. This provides a mechanism by which the fidelity and specificity of the immune system against foreign antigens is improved without increasing the potential for developing an @entity792 .
