HLA-B35 influences the apoptosis rate in human peripheral blood mononucleated cells and HLA-transfected cells.
Human leukocyte antigen (HLA) class I antigens can act as signal-transducing molecules that influence individual reactivity to external stimuli and the existence of haplotype-specific cell signal regulation has been suggested. In this article, we provide definite experimental evidence for the existence of a HLA-B35 haplotype-specific regulation of cell apoptosis in different experimental models. First, we demonstrated that HLA-B35, but not other HLA-class I antigens, was associated with an increased cell susceptibility to apoptosis in human peripheral mononuclear cells (PBMCs) exposed in vitro to thapsigargin. Second, we confirmed this association in human ECV 304 cells transfected with HLA-B35 or with HLA-B8, an antigen that did not appear to influence the apoptosis rate in the thapsigargin-treated PBMCs. Third, we confirmed the specific influence of HLA-B35 on cell apoptosis in non human cells (i.e., HLA-B35-transfected NIH3T3 murine fibroblasts). Our data show the existence of HLA-B35 haplotype-specific regulation of cell apoptosis and open new perspectives on the role of HLA class I genes in cell activation and disease susceptibility.
Salazar
Giulia
G
Unit of Clinical Immunology and Allergology, University of Milano and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy.
Colombo
Gualtiero
G
Lenna
Stefania
S
Antonioli
Rita
R
Beretta
Lorenzo
L
Santaniello
Alessandro
A
Scorza
Raffaella
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015797:HLA-B35 Antigen / Q000235:genetics / Q000502:physiology*; D015795:HLA-B8 Antigen / Q000235:genetics / Q000502:physiology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells / Q000166:cytology / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D015797:HLA-B35 Antigen; D015795:HLA-B8 Antigen; D011993:Recombinant Fusion Proteins; D019284:Thapsigargin