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Differential immunodominance of individual MHC locus products: Implications for the induction of immunologic tolerance to allografts
ELSEVIER
Differential lmmunodominance of Individual MHC Locus Products: Implications for the Induction of Immunologic Tolerance to Allografts D. Saitovitch,
D. Roelen, P.J. Morris, and K.J. Wood
I
N CLINICAL organ transplantation, a hierarchy in the immunodominance of the products of some HLA loci has been established. Matching for some of these antigens, HLA-DR and HLA-B, has been extensively demonstrated to be more positively related to graft function than matching for others, such as HLA-DQ.‘-” We have shown in a mouse model that the class I H2 Kh molecules are more tolerogenic than H2 Db molecules.435 METHODS C3HIHe mice (H2k) were pretreated IV with blood from C57BWlO mice (H2h) or with syngeneic L cells expressing Kh or D” molecules. FACS assays to assess antibody formation and CTLp frequency assays for both donor class I MHC molecules Kh or D” were
of transplantation tolerance. The knowledge of the immunodominant MHC molecules in a specific population may allow more effective strategies for the induction of tolerance in clinical transplantation to be designed.
REFERENCES
1. Poli F, Scalamogna M, Mascaretti L, et al: Transplantation 56:97, 1993 2. Beckingham IJ, Dennis MJ, Bishop MC, et al: Br J Surg 81574, 1994 3. Thorogood J, Persijn GG, Schreuder GM, et al: Transplantation 50:146, 1990
performed 28 days later.
4. Madsen JC, Superina RA, Wood KJ, et al: Nature 332:161, 1988
RESULTS
5. Saitovitch D, Morris PJ, Wood KJ: Transplantation 1996
C57BWlO blood transfusion induced twofold higher levels of anti-Kb compared to anti-D’ IgG antibodies. Likewise, the anti-Kb CTLp frequency was between twofold and as much as sixfold higher than the anti-D’ response. Similarly, L-K’ cells proved to be much more immunogenic than L-D’ cells using this analysis. CONCLUSIONS
Immunodominant MHC molecules induce stronger alloimmune responses and are more effective in the induction
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
61:1532,
From the Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK. D.S. is a Research Fellow supported by CAPES (Brazilian government). Address reprint requests to K.J. Wood, Nuffield Department of Surgery, John Radcliffe Hospital Headington, Oxford, OX3 9DU, UK.
0041-l 345/97/$17.00 PII SO041 -1345(96)00549-O
1443
Transplantation
Proceedings,
29, 1443 (1997)
Differential lmmunodominance of Individual MHC Locus Products: Implications for the Induction of Immunologic Tolerance to Allografts D. Saitovitch,
D. Roelen, P.J. Morris, and K.J. Wood
I
N CLINICAL organ transplantation, a hierarchy in the immunodominance of the products of some HLA loci has been established. Matching for some of these antigens, HLA-DR and HLA-B, has been extensively demonstrated to be more positively related to graft function than matching for others, such as HLA-DQ.‘-” We have shown in a mouse model that the class I H2 Kh molecules are more tolerogenic than H2 Db molecules.435 METHODS C3HIHe mice (H2k) were pretreated IV with blood from C57BWlO mice (H2h) or with syngeneic L cells expressing Kh or D” molecules. FACS assays to assess antibody formation and CTLp frequency assays for both donor class I MHC molecules Kh or D” were
of transplantation tolerance. The knowledge of the immunodominant MHC molecules in a specific population may allow more effective strategies for the induction of tolerance in clinical transplantation to be designed.
REFERENCES
1. Poli F, Scalamogna M, Mascaretti L, et al: Transplantation 56:97, 1993 2. Beckingham IJ, Dennis MJ, Bishop MC, et al: Br J Surg 81574, 1994 3. Thorogood J, Persijn GG, Schreuder GM, et al: Transplantation 50:146, 1990
performed 28 days later.
4. Madsen JC, Superina RA, Wood KJ, et al: Nature 332:161, 1988
RESULTS
5. Saitovitch D, Morris PJ, Wood KJ: Transplantation 1996
C57BWlO blood transfusion induced twofold higher levels of anti-Kb compared to anti-D’ IgG antibodies. Likewise, the anti-Kb CTLp frequency was between twofold and as much as sixfold higher than the anti-D’ response. Similarly, L-K’ cells proved to be much more immunogenic than L-D’ cells using this analysis. CONCLUSIONS
Immunodominant MHC molecules induce stronger alloimmune responses and are more effective in the induction
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
61:1532,
From the Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK. D.S. is a Research Fellow supported by CAPES (Brazilian government). Address reprint requests to K.J. Wood, Nuffield Department of Surgery, John Radcliffe Hospital Headington, Oxford, OX3 9DU, UK.
0041-l 345/97/$17.00 PII SO041 -1345(96)00549-O
1443
Transplantation
Proceedings,
29, 1443 (1997)