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MHC Class I Phenotype and Function of Human β 2 ‐Microglobulin Transgenic Murine Lymphocytes
Author(s) -
BJERAGER L.,
PEDERSEN L. Ø.,
BREGENHOLT S.,
NISSEN M. H.,
CLAESSON M. H.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1996.d01-358.x
Subject(s) - beta 2 microglobulin , phenotype , transgene , genetically modified mouse , mhc class i , function (biology) , biology , class (philosophy) , major histocompatibility complex , microbiology and biotechnology , immunology , genetics , gene , computer science , artificial intelligence
Lymphoid cells from β 2 ‐microglobulin (β 2 m) knockout mice transgenic for human (h) β 2 m (C57BL/10 mβ 2 m − /hβ 2 m + ) were compared with normal mice for their binding to exogenously added hβ 2 m, binding to a H‐2D b peptide and for functional activity in a one‐way allogenic MLC. Based on data from cellular binding studies, Scatchard analyses and flow cytometry, it is concluded that exogenous hβ 2 m does not bind to hybrid MHC class I (MHC‐I) molecules composed of mouse heavy chain/hβ 2 m molecules expressed on lymphocytes of transgenic mice. Immunoprecipitation and SDS‐PAGE analysis of metabolically labelled normal C57BL/6 lymph node cells showed binding of exogenous hβ 2 m to MHC‐I, in particular, to the H‐2D b molecule through an exchange with endogenous mouse β 2 m. In contrast to normal H‐2D b molecules, hybrid H‐2D b expressed on the surface of transgenic lymphocytes binds radiolabelled peptide in the absence of exogenous added hβ 2 m suggesting that a stable fraction of hybrid H‐2D b molecules is empty or contain peptides with very low affinity. In a one‐way allogenic mixed lymphocyte culture, transgenic splenocytes were found to be far less stimulatory than normal splenocytes. In contrast, transgenic alloreactive cytotoxic T lymphocytes developed earlier in MLC than their non‐transgenic counterparts. These data indicate that the hybrid mouse heavy chain/hβ 2 m complex alters the alloantigenic repertoire and influences important aspects of T‐cell activation.