The Major Histocompatibility Complex in Man

Dausset, J

doi:10.1126/science.6792704

Cited by 207 publications

(76 citation statements)

References 39 publications

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“…The major histocompatibility complex (MHC) comprises an array of genes located on chromosome 6 in humans and encodes several sets of immunoregulatory molecules-the classical transplantation antigens (class I), the immune response-associated antigens (class II) and complement genes (class III) (Dausset, 1981). MHC class I molecules are polymorphic transmembrane glycoproteins composed of two polypeptide chains.…”

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confidence: 99%

Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer

Korkolopoulou

Kaklamanis²,

Pezzella³

et al. 1996

Br J Cancer

164

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Summary Presentation of endogenous antigenic peptides to cytotoxic T lymphocytes is mediated by the major histocompatibility complex (MHC) class I molecules. For the stable assembly of MHC class I complex it is necessary that the antigenic peptide is transported by the MHC-encoded transporters TAP-1 and TAP-2 into a pre-Golgi region. T-cell-mediated host-vs-tumour response might therefore depend on the presence of these molecules on tumour cells. The presence of MHC class I antigens and TAP-1 was studied in a series of 93 resection specimens of non-small-cell lung carcinomas (NSCLCs) by immunohistochemical methods using antibodies against the assembled class I molecule, beta2-microglobulin (02-m), heavy-chain A locus, A2 allele and TAP-1 protein. Eighty-six patients were included in the survival analysis. Total loss of class I molecule was observed in 38% of the cases and was usually accompanied by loss of ,2-m and of heavy chain A locus. Selective loss of A locus was seen in 8.3% and of A2 allele in 27% of the cases. TAP-1 loss was always combined with P2-m and/or heavy chain A locus loss. No correlation was found between the expressional status of any of the above molecules, including the selective A2 allelic loss and histological type, degree of differentiation, tumoral stage, nodal stage and survival. Our findings suggest that loss of antigen-presenting molecules (including both MHC class I alleles and TAP-1) is a frequent event in lung cancer. However, the immunophenotypic profile of MHC class I and TAP-1 seems to be unrelated in vivo to the phenotype, growth or survival of NSCLC.

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confidence: 99%

Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer

Korkolopoulou

Kaklamanis²,

Pezzella³

et al. 1996

Br J Cancer

164

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“…These antigens are controlled by a cluster of genes located in chromosome 17 in mice and chromosome 6 in humans. These genes code for the classical transplantation antigens (class I), the immune response associated antigens (class II) and complement genes (class III) (Dausset, 1981). Class I antigens are cell surface glycoproteins composed of a highly polymorphic heavy chain (Mr 45,000) associated in a non-covalent way to fl2-microglobulin (Ploegh et al, 1981).…”

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confidence: 99%

HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas

Esteban²,

Ferrón³

et al. 1989

Br J Cancer

118

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Summary The expression of HLA class I antigens was studied in 99 primary tumours (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: + / -, + / +, -/ +, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples.

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“…Human leucocyte antigens or histocompatibility genes have been revealed to have so enormous polymorphism as well as important immunological functions, particularly surveillance of external agents against cell (Frelinger and Schreffer, 1975;Bodmer, 1972;Bodmer and Bodmer, 1978;Barnstable et aI., 1979;Dausset, 1981, andThomson 1981), that HLA could be very useful as a genetic marker to disentangle genetic mechanism involved in onset of disease, assuming that the association between HLA and disease was due to linkage disequilibrium.…”

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confidence: 99%