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Major Histocompatibility Complex Molecules (major + histocompatibility_complex_molecule)

Distribution by Scientific Domains
Medical Sciences80%

Selected Abstracts

IDENTIFYING COEVOLUTIONARY PATTERNS IN HUMAN LEUKOCYTE ANTIGEN (HLA) MOLECULES

EVOLUTION, Issue 5 2010
Xiaowei Jiang
The antigenic peptide, major histocompatibility complex molecule (MHC; also called human leukocyte antigen, HLA), coreceptor CD8, or CD4 and T-cell receptor (TCR) function as a complex to initiate effectors' mechanisms of the immune system. The tight functional and physical interaction among these molecules may have involved strong coevolution links among domains within and between proteins. Despite the importance of unraveling such dependencies to understand the arms race of host,pathogen interaction, no previous studies have aimed at achieving such an objective. Here, we perform an exhaustive coevolution analysis and show that indeed such dependencies are strongly shaping the evolution and probably the function of these molecules. We identify intramolecular coevolution in HLA class I and II at domains important for their immune activity. Most of the amino acid sites identified to be coevolving in HLAI have been also detected to undergo positive Darwinian selection highlighting therefore their adaptive value. We also identify coevolution among antigen-binding pockets (P1-P9) and among these and TCR-binding sites. Conversely to HLAI, coevolution is weaker in HLAII. Our results support that such coevolutionary patterns are due to selective pressures of host,pathogen coevolution and cooperative binding of TCRs, antigenic peptides, and CD8/CD4 to HLAI and HLAII. [source]

Peptide-induced suppression of collagen-induced arthritis in HLA,DR1 transgenic mice

ARTHRITIS & RHEUMATISM, Issue 12 2002
Linda K. Myers
Objective To identify peptides capable of altering the immune response to type II collagen (CII) in the context of HLA,DR. Methods Immunizing mice transgenic for the human HLA,DRB1*0101 immune response gene with CII elicits an arthritis (collagen-induced arthritis [CIA]) that resembles rheumatoid arthritis. We have previously identified an immunodominant determinant of CII, CII (263,270), recognized by T cells in the context of DR1. To produce synthetic peptides with the potential of disrupting the DR1-restricted immune response, synthetic analog peptides were developed that contain site-directed substitutions in critical positions. These peptides were used to treat CIA in DR1 transgenic mice. Results An analog peptide, CII (256,276, N263, D266), that inhibited T cell responses in vitro, was identified. When DR1 mice were coimmunized with CII and CII (256,276, N263, D266), the incidence and severity of arthritis were greatly reduced, as was the antibody response to CII. Moreover, CII (256,276, N263, D266) was effective in down-regulating the immune responses to CII and arthritis, even when administered 2 weeks following immunization with CII. Spleen and lymph node cells from CII-immunized mice cultured with CII (256,276, N263, D266) in vitro produced increased amounts of interleukin-4 (IL-4) compared with cells cultured with the wild-type peptide, CII (256,276). Furthermore, CII (256,276, N263, D266) was incapable of preventing arthritis in DR1 IL-4,/, mice (genetically deficient in IL-4). Conclusion These data establish that CII (256,276, N263, D266) is a potent suppressor of the DR-mediated immune response to CII. Its effect is mediated, at least in part, by IL-4. These experiments represent the first description of an analog peptide of CII recognized by T cells in the context of a human major histocompatibility complex molecule that can suppress autoimmune arthritis. [source]

Interplay between T helper type 1 and type 2 cytokines and soluble major histocompatibility complex molecules: a paradigm in pregnancy

IMMUNOLOGY, Issue 3 2002
I. Athanassakis
No abstract is available for this article. [source]

Canine diabetes mellitus: from phenotype to genotype

JOURNAL OF SMALL ANIMAL PRACTICE, Issue 1 2008
B. Catchpole
Breed differences in susceptibility to diabetes mellitus in dogs suggest an underlying genetic component to the pathogenesis of the disease. There is little evidence for an equivalent of human type 2 diabetes in dogs, and it has been proposed that canine diabetes is more comparable to the type 1 form of the disease. Certain immune response genes, particularly those encoding major histocompatibility complex molecules involved in antigen presentation, are important in determining susceptibility to human type 1 diabetes. We tested the hypothesis that canine major histocompatibility complex genes (known as the dog leucocyte antigen) are associated with diabetes in dogs. A total of 530 diabetic dogs and more than 1000 controls were typed for dog leucocyte antigen, and associations were found with three specific haplotypes. The DLA-DRB1*009/DQA1*001/DQB1*008 haplotype shows the strongest association with diabetes in the UK dog population. This haplotype is common in diabetes-prone breeds (Samoyed, cairn terrier and Tibetan terrier) but rare in diabetes-resistant breeds (boxer, German shepherd dog and golden retriever), which could explain differences in the prevalence of diabetes in these different breeds. There is evidence that the DLA-DQA1*001 allele is also associated with hypothyroidism, suggesting that this could represent a common susceptibility allele for canine immune-mediated endocrinopathies. [source]

How to outwit the enemy: dendritic cells face Salmonella,

APMIS, Issue 9 2006
Review article
Salmonella enterica serovar Typhi causes typhoid fever, a serious life-threatening systemic infection. In mice, a similar disease is caused by Salmonella enterica serovar Typhimurium. During typhoid fever, soon after attachment to the mucosal surface of the gut, bacteria come into contact with the dendritic cells (DCs). The ability to sample antigens, process and present them to na,Šve and mature T cells, in the context of major histocompatibility complex molecules, makes DCs indispensable for mounting a specific and efficient immune response to invading pathogens. These bacteria, however, have evolved a number of mechanisms to interfere with or subvert DC functions. This review aims to describe how Salmonella clashes with dendritic cells at different stages of infection as well as the war strategies of these two opposing sides. [source]