Peptide-mhc-immunoglobulin multimers and methods of use thereof
OwnerThomas J. MALIA, Joanna F. SWAIN +2inventors
InventorsThomas J. MALIA, Joanna F. SWAIN, Andrew G. HAMEL, Ellen M. WHITE
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Abstract
Multimers are provided in which a Major Histocompatibility Complex (MHC) class I or class II molecule, optionally complexed with an MHC-binding peptide, is attached to a multimerization moiety from immunoglobulin M or A (IgM or IgA) to thereby create a multivalent peptide-MHC-Ig multimer composition. The multimers can be used, for example, to determine the binding specificity of T cell receptors, such as for particular MHC-peptide complexes. The multimers can also be used, for example, to modulate an immune response in a subject by administering the multimer to the subject. Methods of making the peptide-MHC-Ig multimers are also provided.
Claims107
A multimer comprising a Major Histocompatibility Complex (MHC) moiety operatively linked to a multimerization moiety, wherein:
- (a) the MHC moiety comprises an MHC molecule optionally bound with a cognate peptide;
- and
- (b) the multimerization moiety comprises (i) an IgM Cμ4 constant region and a tailpiece region;
- or (ii) an IgA Cα3 constant region and a tailpiece region, wherein the tailpiece region in (b)(i) or (b)(ii) is an IgM tailpiece region or an IgA tailpiece region.
A multimer comprising a Major Histocompatibility Complex (MHC) moiety operatively linked to a multimerization moiety, wherein:
- (a) the MHC moiety comprises (i) an MHC Class I molecule, optionally bound with an MHC Class I-binding peptide;
- or (ii) an MHC Class II molecule, optionally bound with an MHC Class II-binding peptide;
- and
- (b) the multimerization moiety comprises an IgM tailpiece region or an IgA tailpiece region.
The multimer of 22 or 23, wherein the first and/or second heterodimerization motifs comprise a leucine zipper.
An isolated nucleic acid molecule, encoding a Major Histocompatibility Complex (MHC) moiety operatively linked to a multimerization moiety, wherein:
- (a) the MHC moiety comprises an MHC molecule and optionally a cognate peptide;
- and
- (b) the multimerization moiety comprises (i) an IgM Cμ4 constant region and a tailpiece region;
- or (ii) an IgA Cα3 constant region and a tailpiece region, wherein the tailpiece region in (b)(i) or (b)(ii) is an IgM tailpiece region or an IgA tailpiece region.
An isolated nucleic acid molecule, encoding a Major Histocompatibility Complex (MHC) moiety and, optionally, an MHC binding peptide, and which MHC moiety is operatively linked to a multimerization moiety, wherein:
- (a) the MHC moiety comprises (i) an MHC Class I molecule, and, optionally an MHC Class II binding peptide;
- or (ii) an MHC Class II molecule and, optionally, an MHC Class II binding peptide;
- and
- (b) the multimerization moiety comprises (i) an IgM Cμ4 constant region and a tailpiece region;
- or (ii) an IgA Cα3 constant region and a tailpiece region, wherein the tailpiece region in (b)(i) or (b)(ii) is an IgM tailpiece region or an IgA tailpiece region.
An isolated nucleic acid molecule encoding a Major Histocompatibility Complex (MHC) moiety and, optionally, an MHC binding peptide, wherein:
- (a) the MHC moiety comprises (i) an MHC Class I molecule and, optionally, an MHC Class I binding peptide;
- or (ii) an MHC Class II molecule and, optionally, an MHC Class II binding peptide;
- and
- (b) the multimerization moiety comprises an IgM tailpiece region or an IgA tailpiece region.
Dependencies are inferred from the claim text.