Specificity and frequency of primary anti-HLA cytotoxic T lymphocytes in normal and HLA-B27.2-, HLA-B27.5-, and HLA-Cw3-transgenic mice. A transgenic model for MHC xenoantigen recognition.
Previous studies have shown that the lymphocytes of naive mice produce a strong primary CTL responses in vitro to human MHC class I Ag presented by HLA-transgenic mouse (TGM) cells. A limiting dilution (LD) assay was used to analyze this xenoreactive CTL repertoire in mice. Frequencies of HLA class I-specific CTL precursors (CTLp) were estimated in naive normal and HLA-B27.2-, -B27.5- and HLA-Cw3-double TGM (i.e., mice expressing HLA and human beta 2-microglobulin (hu beta 2m]. The xenoreactive CTLp frequencies were compared to frequencies of CTLp to H-2 alloantigens estimated in naive normal mice. The results showed that the frequencies of HLA class I-specific CTLp are comparable with those of alloreactive CTLp. This overlap in CTLp frequencies suggests that HLA class I xenoantigens are recognized by primary mouse CTL as allelic variants of H-2K and H-2D. This was confirmed in split well analysis by the observation that the xenoreactive response was not restricted by self-MHC of the responding mouse. Thus, primary HLA class I-specific mouse CTL clones recognized their target Ag regardless of whether they were expressed on H-2-mismatched mouse cells or on human cells. The frequencies of HLA class I-specific CTLp in HLA-TGM were comparable to those in normal mice. We propose that MHC allo- and xenoreactive CTL responses are not caused by the activation of CTLp specific for self-MHC plus peptide but to the activation of CTLp recognizing MHC allo- and xenoantigens directly or as peptides presented by their native MHC molecules.
Kievits
F
F
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Boerenkamp
W J
WJ
Lokhorst
W
W
Ivanyi
P
P
D000818:Animals; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000166:cytology; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006183:H-2 Antigens; D006680:HLA Antigens; D015796:HLA-B27 Antigen; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen