Alien antigens return to the fold

Parham, Peter

doi:10.1016/0167-5699(89)90326-5

Cited by 10 publications

(3 citation statements)

References 42 publications

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“…However, this mutation does not create a new antigenic peptide, but rather modifies the structure of the HLA-A2 molecule which now appears to be recognized per se. The ability o f altered M H C molecules to act as tumor-specific antigens has been extensively debated, starting with observations by Invernizzi and Parmiani (41,42). The mutated HLA-A2 molecule described here is the first instance of a somatic point mutation changing an amino acid in a M H C class I molecule, thereby transforming it into a target structure that is recognized by autologous CTL.…”

Section: Discussionmentioning

confidence: 99%

A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma.

Brändle

Brasseur

Weynants

et al. 1996

The Journal of Experimental Medicine

120

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SummaryMany human tumor ceils have been shown to express antigens that are recognized by autologous cytotoxic T lymphocytes (CTL) and the molecular nature era number of melanoma antigens has been defined recendy. Here we describe the characterization of an antigen recognized on a renal ceil carcinoma by autologous CTL clones. This antigen is encoded by the HLA-A2 gene present in the tumor cells. The sequence of this gene differs from the HLA-A2 sequence found in autologous peripheral blood lymphocytes by a point mutation that results in an arginine to isoleucine exchange at residue 170, which is located on the a-helix of the ct2 domain. Transfection experiments with the normal and mutated HLA-A2 cDNA demonstrated that this amino acid replacement was responsible for the recognition of the HLA-A2 molecule expressed on the tumor cells. The mutant HLA-A2 gene was also detected in the original tumor tissue from the patient, excluding the possibility that the mutation had appeared in vitro. Thus, HLA class I molecules carrying a tumor-specific mutation can be involved in the recognition of tumor cells by autologous CTL.

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Section: Discussionmentioning

confidence: 99%

A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma.

Brändle

Brasseur

Weynants

et al. 1996

The Journal of Experimental Medicine

120

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“…The immunogenicity of one UV-induced sarcoma has been traced to a class-I MHC molecule related to the Ld antigen (Stauss et al, 1986). However, these antigens are not representative of tumour-specific antigens since the sarcoma used by Stauss et al (1591) was no doubt contaminated and was not strictly of C3H origin (Parham, 1989;Lee et al, 1988). Lurquin et al (1989), working with the chemically-induced antigens of the mast-cell tumour, P8 15, have reported the complete structure of gene conferring expression of turn-antigen P91A; its sequence shows no significant similarity with sequences in current data bases.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of a serologically defined tumour membrane antigen from a chemically‐induced rat sarcoma, HSN

Léger

Dunn

Coles

et al. 1991

Intl Journal of Cancer

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Polypeptides containing the tumour antigenic determinant present on the external domain of a membrane antigen of the 3-4 benzpyrene-induced rat fibrosarcoma HSN have been isolated and purified. Following cleavage from intact cells with trypsin, the peptides were purified by immunoaffinity chromatography and SDS-PAGE. Three polypeptides of molecular weight 120, 45 and 42 kDa were obtained that bound the specific rat monoclonal antibody (MAb) 11/160 in Western blots. Chemical analyses of the 45-kDa fragment yielded the following sequence: NH2-I V F P H G S L M V I L E H T Q K P All 14 of the syngeneic MAbs prepared from rats bearing the HSN tumour competed with each other to bind to the specific antigen. Western blots of the purified tryptic fragments probed with 125I-AbI revealed that, while some of the MAbs (11/160, ALN/12/17 and ALN/9/94) recognized a sequential determinant, others (ALN/11/53, ALN/16/53, and AL/3/12) bound to a conformational epitope. It is concluded that the AbI bind to distinct but overlapping epitopes.

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“…While only sequencing the 3' ends of the genes encoding 0 4 and Lq and the complete characterization of the Ks gene can unequivocally demonstrate their complete identity, or lack thereof, to the tumour genes, the most rational explanation for the immunogenicity of 1591 is that it is allogeneic in origin (Parham, 1989). In addition, analyses of the primary structures of these novel molecules can provide insights into the possible molecular basis of their differential expression and CTL recognition.…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of H‐2 Class I Molecules Expressed on the Uv‐induced Tumour 1591

McKinney

McMillan

1990

Int J Immunogenetics

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SUMMARY We have biochemically characterized by 2D (two‐dimensional) electrophoresis three novel class I molecules called A166, A149 and A216 expressed by 1591, a UV‐induced fibrosarcoma, and have compared them to class I molecules expressed by mice of the H‐2q and H‐2s haplotypes. A166 and A149 are very similar if not identical to Dq and Lq respectively. We have shown, using HPLC (high‐pressure liquid chromatography) tryptic peptide mapping, that the expression of A166 is approximately three fold greater than A149, reminiscent of Dd compared to Ld. In addition A216 possess an identical isoelectric point to that of the Ks molecule. We demonstrate that outbred Swiss Webster mice express an analogous constellation of class I molecules and we conclude that our results can be most easily interpreted in terms of an allogeneic origin for the novel class I molecules expressed on 1591.

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Alien antigens return to the fold

Cited by 10 publications

References 42 publications

A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma.

A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma.

Isolation and characterization of a serologically defined tumour membrane antigen from a chemically‐induced rat sarcoma, HSN

Molecular Analysis of H‐2 Class I Molecules Expressed on the Uv‐induced Tumour 1591

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