FREQUENCY OF DOWN-REGULATION OF INDIVIDUAL HLA-A AND HLA-B ALLELES INCERVICAL CARCINOMAS IN RELATION TO TAP-1 EXPRESSION

The development of cervical carcinoma is strongly associated with spec ific types of human papillomaviruses (HPVs). A role for cellular immun ity in cervical disease is supported by the increased occurrence of HP V-associated lesions in immunosuppressed individuals. Upon viral infec tion or malignant transformation, ensuing alterations in gene expressi on result in the generation of novel sets of peptides which can form c omplexes with specific HLA class I heavy chains and beta(2)-microglobu lin. These are then expressed at the cell surface as potential targets for specific T cells. In this study of 100 carcinomas HLA-A and -B cl ass I expression by the tumour cells was down-regulated at one or more alleles in at least 73% of cervical carcinomas. Interference with the transporter associated with antigen presentation (TAP), which translo cates cytosolic peptides from endogenously synthesised proteins (e.g. viral) into the lumen of the endoplasmic reticulum was found in 38% of the HLA class I down-regulated tumours. Loss of expression for common HLA class I alleles ranged from 36% to 71%, and such changes might be expected to influence specific immunogenic peptide presentation and c onsequent immune recognition. These results underline the importance o f single as well as multiple allelic loss in cervical neoplasia and ha ve important implications for attempts to intervene immunologically in cervical cancer.