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Phosphorylcholine‐binding hybridoma proteins of normal and idiotypically suppressed BALB/c mice. II. Variable region N‐terminal amino acid sequences
Author(s) -
Kocher Hans P.,
Berek Claudia,
Schreier Max H.,
Cosenza Humberto,
Jaton JeanClaude
Publication year - 1980
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830100408
Subject(s) - idiotype , phosphorylcholine , biology , isotype , microbiology and biotechnology , antibody , myeloma protein , immunoglobulin light chain , peptide sequence , monoclonal antibody , gene , biochemistry , immunology
Abstract The murine repertoire of anti‐phosphorylcholine (PC) antibodies which do not share the TEPC 15 idiotype was analyzed by partial N‐terminal amino acid sequence determination of the variable (V) regions of five homogeneous IgM PC‐specific antibodies, which were produced by cell fusion of TEPC 15‐suppressed BALB/c spleen cells with X63‐Ag8 myeloma cells. The heavy (H) chains of three of them, HPC 16, 35 and 126, expressed an identical N‐terminal sequence (residues 140) to the TEPC 15 and all other PC‐binding myeloma proteins (PCBMP). The other two (HPC 19, 104) belonged to a new V H isotype, tentatively designated V H‐12 , not seen in the library of PCBMP nor in any mouse V H region known so far. The first hypervariable region of HPC 19 and 104 was different from all those known among PCBMP, thus suggesting that the V H‐12 isotype is coded for by a separate germ‐line gene. The variable regions of the light chains (V L ) displayed all V, isotypes known in PCBMP, with the exception of the V, isotype of TEPC 15. In addition, one PC‐binding hybridoma protein had the light chain isotype of the parental myeloma immunoglobulin. In the hybridoma IgM antibodies, new V H ‐V L combinations not encountered among PCBMP, as well as known V H ‐V L pairings of PCBMP, were expressed. The data suggest that a limited number of V H and V L regions scramble to generate the various PC‐specific antibodies. Thus, the diversity of the murine repertoire of anti‐PC antibodies may be explained at least in part by a nongenetic mechanism of VH‐V L combinatorial association.