摘要:

T cells can recognize foreign MHC antigens by two distinct routes, either directly as intact molecules, or indirectly as processed peptides. Recent evidence strongly suggests that the indirect pathway of allorecognition plays a key role in initiating and sustaining graft rejection. Theoretically, all mismatched HLA alloantigens could generate immunogenic peptides which may be recognized in the context of any of the two self HLA-DR molecules. However, indirect recognition appears to be limited to a single peptide determinant of an allogeneic HLA-DR molecule and restricted by one self HLA-DR molecule. Furthermore, T cells involved in the self-restricted allopeptide recognition express a limited array of T cell receptor variable genes. These findings suggest that selective immune interventions, such as peptide blockade of the self HLA-DR molecule involved in the presentation of the dominant allopeptide, induction of high-zone tolerance or TCR antagonism, may be devised to prevent graft rejection.

ISSN:0883-0185    

DOI:10.3109/08830189609061745

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Elucidation of the structure of MHC molecules has provided profound new insights into their function in antigen presentation. In addition, structural studies have implicated certain regions of MHC molecules in specific functions. Although much of MHC biology has concentrated on the extensive polymorphism among these molecules, there is also evolutionary pressure to maintain the relatively monomorphic portions of these molecules. Drs. Krensky and Clayberger have found that synthetic peptides corresponding to linear sequences of HLA molecules have immunomodulatory effects bothin vitroandin vivo.In this paper, they review the structure of HLA molecules and their studies of HLA derived peptides as novel immunotherapeutics. Members of the heat shock protein 70 family are implicated in the HLA derived peptide immunosuppressive pathway.

ISSN:0883-0185    

DOI:10.3109/08830189609061746

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

A large number of alloantigenic determinants could be generated by both the direct and indirect alloantigen presentation pathways. Hence, a heterogeneous population of T cells expressing a wide variety of receptors would be expected to respond to this diverse array of alloantigenic determinants. However, T cells expressing highly restricted T cell receptor (TCR) variable genes have been reported in a variety of alloimmune responses. A similar phenomenon has been observed in a wide variety of other immune responses, from those induced by superantigens, to very specific responses induced by a single peptide presented by a single MHC molecule. Given this scenario, the limited number of T cell clones which dominate an allograft rejection response, or for that matter an autoimmune response or a tumor specific response, could be therapeutically targeted by virtue of the selected TCR expression.

ISSN:0883-0185    

DOI:10.3109/08830189609061747

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The DMαand DMβgenes encode a nonpolymorphic, class II-like molecule which functions by an, as yet, undefined mechanism in the assembly of Major Histocompatibility Complex class II-peptide complexes. Indeed, mutant cells which express class II molecules but fail to express DM are unable to process and present native protein antigens. A striking phenotype of the mutation is class II molecules that contain almost exclusively a nested set of invariant chain peptides, termed CLIP, for class II associated Ii peptides, instead of the normal array of endogenously and exogenously derived peptides. Thus, DM appears to be required for the correct assembly of processed antigen-class II complexes. Recently, the subcellular compartments that contain DM and in which functional processed antigen-class II complexes are first formed have been described. Here, the evidence for the function of DM in the antigen-processing compartments is reviewed.

ISSN:0883-0185    

DOI:10.3109/08830189609061748

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189609061749

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189609061750

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Allograft rejection has been attributed predominantly to alloreactive T cells which recognize intact allogeneic MHC on donor antigen presenting cells (APC). Following transplantation, T cells may also recognize donor derived MHC antigens which have been processed and presented as antigenic peptides in the context of self-MHC by recipient APC-so called indirect allorecognition. This article discusses the possible role of indirect T cell recognition in the graft rejection response with particular emphasis on recent experimental data obtained fromin vivotransplant models. Although the relative contribution of indirect allorecognition to the rejection process remains unclear the available evidence suggests that the contribution of self-MHC restricted T cells to graft rejection may have been underestimated.

ISSN:0883-0185    

DOI:10.3109/08830189609061751

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor