The Multifactorial Nature of MHC-Linked Susceptibility to Insulin-Dependent Diabetes
作者:
SeguradoOscar G.,
ArnaizAntonio,
WankRudolf,
SchendelDolores J.,
期刊:
Autoimmunity
(Taylor Available online 1993)
卷期:
Volume 15,
issue 1
页码: 85-89
ISSN:0891-6934
年代: 1993
DOI:10.3109/08916939309004844
出版商: Taylor&Francis
关键词: Major histocompatibility complex;insulin-dependent diabetes mellitus;HLA haplotypes;peptide processing;T-cell tolerance;virus
数据来源: Taylor
摘要:
Several lines of evidence suggest that major histocompatibility complex (MHC)-linked susceptibility to insulin-dependent diabetes mellitus (IDDM) is not restricted to the presence or absence of any single gene product. The existence of population-specific haplotypes associated with IDDM supports the concept that distinct combinations of MHC alleles interact synergistically to induce disease when other environmental and genetic factors are present. MHC-controlled peptide transport and binding to MHC molecules as well as the levels of MHC class I and class II expression in the thymus and pancreaticβcells may also play significant roles in the outbreak of IDDM. These intrinsic factors shape the T-cell receptor (TCR) repertoire during T-cell ontogeny in the thymus and later influence the efficiency of potentially autoreactive T cells in the periphery. Several extrinsic factors, such as viruses or dietary proteins, may be directly involved in the TCR/MHC interaction at the cell surface; furthermore viruses can alter the regulatory mechanisms of peptide/MHC interaction and expression. We propose that these intrinsic and extrinsic factors need not be mutually exclusive and might even be interdependent: a given virus may act deleteriously only when certain autoreactive T cells and combinations of MHC alleles are present in the individual. IDDM would develop if pathogenic T-cells are activated and an appropriate target MHC/peptide is expressed in pancreaticβcells. Future knowledge of the host-virus relationships influenced by the MHC genes, the function of their encoded proteins and the polymorphic gene structure of well-established susceptibility MHC haplotypes will help delineate an overall picture of this issue.
点击下载:
PDF (503KB)
返 回