Immunogenetics of human minor histocompatibility antigens: their polymorphism and immunodominance

Abstract

Minor Histocompatibility (mH) antigens are polymorphic endogenously synthesized products that can be recognized by alloreactive T cells in the context of major histocompatibility complex molecules. In transplant situations where tissue donor and recipient are matched for HLA, mH antigens may trigger strong cellular immune responses. To gain insight into the polymorphism of mH antigens we studied their frequencies in the healthy population. Five HLA class I restricted mH antigens recognized by distinct cytotoxic T-cell (CTL) clones were used in the population genetic analysis consisting of a panel (N = 100) of HLA typed target cells. Three mH antigens showed phenotype frequencies of 69 % or higher, this contrasted the frequencies of two other mH antigens with 16 and 7% respectively. To gain insight into the "functional" polymorphism of the T-cell response to mH antigens, we analyzed the specificity of CTL clones within individuals. Three out of five individuals investigated shared a CTL response to one single HLA-A2 restricted mH antigen. These results indicate limited allelic polymorphism for some mH antigens in the healthy population and are suggestive of the existence of immunodominant human mH antigens.

Cytokines restore MHC class I complex formation and control antigen presentation in human cytomegalovirus-infected cells

“…The generation and maintenance of the CD8 + CTL clones used in this study was described in detail earlier (De Bueger et al, 1992;Van Els et al, 1992). The CTL clone 3E7 is allo-A2 specific, the clone 1R35 specific for the male H-Y antigen is HLA-A2 restricted, and the clone 5HO11 recognizing the HA-3 mH antigen is HLA-A1 restricted.…”

Clinical consequences of sensitisation to minor histocompatibility antigens before allogeneic bone marrow transplantation

“…ing mHags HA-1 and H-Y was used to determine the specificity of the pre-and post-transplant clones. 22,23 Results…”

“…In patient 2, who rejected after 41 days without being immunised before BMT, the CTL response was directed exclusively against HA-1, the HLA-A‫-1020ء‬restricted mHag frequently recognized. 23,24 All other specificities recognised by the CTL that were assumed to recognise the same mHag when they lysed the same panel cells were designated as minor I-III (Table 2). Three CTL clones with anti-donor activity were not further characterised.…”

Minor histocompatibility antigen-specific T cells with multiple distinct specificities can be isolated by direct cloning of IFNγ-secreting T cells from patients with relapsed leukemia responding to donor lymphocyte infusion

“…The postulated immunodominance of these mHags is based on the frequent detection of T cells specific for these mHags in different patients receiving SCT from their mHag disparate donors. 19,20 However, the in vitro method most commonly used for the detection of mHag-specific T cells, is based on the generation of T-cell lines and subsequent cloning of T cells by limiting dilution. This method may preferentially select for precursor T cells with the most optimal capacity to survive and proliferate in vitro, and may not accurately reflect the variety of mHags involved in the in vivo immune response.…”