Analysis of HLA class Ia transcripts in human leukaemias.
Several leukaemia-specific antigens have been discovered in the recent past, which raised the possibility for T-cell-based immunotherapy for leukaemia. However, failure of such approaches involving interleukin-2 and/or T-cell-based immunotherapy indicated the importance of investigation of the human leucocyte antigen (HLA) status of the haematopoietic malignant cells. Considerable number of reports indicate that both HLA class I and class II are down-regulated in different cases of leukaemias, enabling them to evade immuno-surveillance. However, locus-specific down-regulation in leukaemia has not been widely investigated, although majority of cytotoxic T lymphocyte (CTL) responses are modulated by HLA-A and HLA-B, whereas expression of only HLA-C is unable to block natural killer (NK)-cell-mediated cytotolysis. Therefore, using RT-PCR, we have investigated the HLA class I transcriptional expression in a locus-specific manner, along with HLA-associated accessory molecules beta2-microglobulin and transporter-associated antigen processing molecule (TAP1). Our data suggest that in several newly diagnosed untreated leukaemic patients, HLA-C and beta2-microglobulin are expressed, but not the locus HLA-A or -B. Moreover, TAP1 and beta2-microglobulin were observed to be down-regulated in a number of cases of leukaemia. Our flow cytometric analysis of HLA-ABC also indicates a decrease in mean fluorescent intensity but no complete loss in surface expression of HLA class Ia on the leukaemic cells. Therefore, the observed low surface expression of HLA-ABC may be due to the down-regulation of transcription of HLA-A or -B itself and/or transcriptional suppression of the accessory molecules.
Majumder
Durjoy
D
Biophysics Division, Structural Genomics Section, Saha Institute of Nuclear Physics, Calcutta, India.
Bandyopadhyay
Debasis
D
Chandra
Sarmila
S
Mukhopadhayay
Ashis
A
Mukherjee
Nandini
N
Bandyopadhyay
Subir K
SK
Banerjee
Subrata
S
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D001613:beta 2-Microglobulin / Q000235:genetics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin