Involvement of the chaperone tapasin in HLA-B44 allelic losses in colorectal tumors.

Abstract

Tumors can exhibit selective allelic losses of HLA class I antigens as part of altered HLA phenotypes. In colorectal tumors, the HLA class I allele most frequently lost is HLA-B44, although the precise mechanism responsible for this loss has not been described to date. From a total of 95 colorectal cryopreserved tumor samples, we selected (by immunohistochemical staining) 13 tumors with HLA-B44-negative expression. Loss of heterozygosity at 6p21.3 was demonstrated to be the cause of the negative expression in 4 cases. In the remaining 9 cases, structural analyses of microdissected tissue samples of the 3 subtypes of HLA-B44 loss in these tumors (B*4402, B*4403 and B*4405) did not reveal any mutations. However, all 3 subtypes of HLA-B44 presented in this study shared a common characteristic: the presence of an aspartic amino acid residue at position 114 in the HLA class I heavy chain. This residue has been described as determining tapasin dependence for the surface expression of these alleles and therefore for antigen presentation. We studied tapasin transcription by RT-PCR in these tumors and found tapasin downregulation in all 9 tumors samples with the HLA-B44-negative phenotype. In contrast, tapasin was normally transcribed in HLA-B44-positive colorectal tumors samples, as well as in 3 HLA-B44-negative laryngeal carcinomas and 1 bladder tumor. Defective tapasin transcription seems to be an alteration responsible for the absence of HLA-B44 expression in colorectal tumors, thus contributing to the generation of tumor immune escape phenotypes.

• Authors: Carmen M Cabrera, Miguel-Angel López-Nevot, Pilar Jiménez, Federico Garrido
• Journal: International journal of cancer (Int J Cancer) Vol. 113 Issue 4 Pg. 611-8 (Feb 10 2005) ISSN: 0020-7136 [Print] United States
• PMID: 15455354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiporters
• HLA-B Antigens
• HLA-B44 Antigen
• Immunoglobulins
• Membrane Transport Proteins
• Molecular Chaperones
• tapasin

Topics

• Antiporters (genetics)
• Colorectal Neoplasms (genetics, metabolism)
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Gene Frequency
• HLA-B Antigens (genetics)
• HLA-B44 Antigen
• Humans
• Immunoglobulins (genetics)
• Laryngeal Neoplasms (genetics, metabolism)
• Loss of Heterozygosity
• Membrane Transport Proteins
• Molecular Chaperones
• Reverse Transcriptase Polymerase Chain Reaction
• Urinary Bladder Neoplasms (genetics, metabolism)