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No.55 (PM 4)
The inhibitory effect of serum HLA class I antigens on EBV-specific CD8+CTL in
vitro
N.Erdenesuvd 1,3 , B.Gansuvd 1,2 , B.Munkhbat 1,2 , M.Hagihara 2 , T.Hotta 2 , N.Munkhtuvshin 1 ,
1
Central Scientific Research laboratory, Nat’l Institute of Medicine, Mongolia
2
Department of Transplantation Immunology, Tokai University, Japan
3
Dept. Laboratory Medicine, General Hospital, Uvurkhangai, Mongolia
Objectives: The level of sHLA class I molecules in human sera is markedly increased after BM and
organ transplantation, viral infections, autoimmune disorders and cancer. Their biological and clinical
significance has not been fully studied. In the present study the effects of soluble HLA (sHLA) class I
molecules against EBV-specific CTL were examined.
Materials and Methods: Two different sources of sHLA class I, either bioengineered spliced form of
HLA-B7 (sB7) or natural production from EBV-transformed B cells (natural sHLA), were added during
the induction of CTL or incubated with MHC-restricted CD8+ CTL, which were selected by
immunobeads just before testing for their cytotoxic activity.
Results: Both sB7 and natural sHLA class I blocked the generation of CD+ CTL and also inhibited the
cytotoxic activity of established CTL in a dosedependent manner. In both ways, natural sHLA class I
was effective in 10-fold lover concentrations compared with sB7. The inhibitory effect did not require a
shaping of the HLA allotypes between sHLA and the CTL. CTL, after being treated with sHLA,
underwent apoptosis, which was considered here as the main mechanism. Generally, sHLA class I
consists of three different molecular forms: a shedding form with a heavy chain of 44 kD, a splicing
form with a heavy chain of 35 kD and 37 kD. All these molecules are associated with β2-microglobulin.
Also it was reported that membrane-derived, naturally occurring sHLA class I forms multimers through
the ydrophobic
transmembrane tail, whereas cytosol-derived sHLA class I cannot form aggregates. In our studies, the
naturally sHLA class I consisted of all three different molecular forms of HLA-B7.
Conclusion: The naturally occurring sHLA class I induces apoptosis more markedly than sB7. supports
the same suggestion that the membrane -derived naturally occurring sHLA class I could cross-link with
TCR/CD3 complexes via its multimeric forms, and it probably leads to more effective apoptosis of the
CTL. The difference in the biochemical nature of sHLA class I molecules might be the reason why the
inhibitory effect of naturally occurring sHLA class I as stronger than that of sB7.
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