Steric Hindrance and Fast Dissociation Explain the Lack of Immunogenicity of the Minor Histocompatibility HA-1Arg Null Allele | Zendy

Eric Spierings | Zendy; Stéphanie Gras | Zendy; JeanBaptiste Reiser | Zendy; Bregje Mommaas | Zendy; Mathilde M. Almekinders | Zendy; Michel G.D. Kester | Zendy; Anne Chouquet | Zendy; Madalen Le Gorrec | Zendy; Jan W. Drijfhout | Zendy; Ferry Ossendorp | Zendy; Dominique Housset | Zendy; Els Goulmy | Zendy

Open Access

Steric Hindrance and Fast Dissociation Explain the Lack of Immunogenicity of the Minor Histocompatibility HA-1Arg Null Allele

Author(s) -

Eric Spierings,

Stéphanie Gras,

JeanBaptiste Reiser,

Bregje Mommaas,

Mathilde M. Almekinders,

Michel G.D. Kester,

Anne Chouquet,

Madalen Le Gorrec,

Jan W. Drijfhout,

Ferry Ossendorp,

Dominique Housset,

Els Goulmy

Publication year - 2009

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.0803911

Subject(s) - steric effects , immunogenicity , null allele , minor allele frequency , allele , dissociation (chemistry) , genetics , histocompatibility , biology , chemistry , antigen , stereochemistry , human leukocyte antigen , allele frequency , gene

The di-allelic HLA-A2 restricted minor histocompatibility Ag HA-1 locus codes for the highly immunogenic HA-1(His) and the nonimmunogenic HA-1(Arg) nonapeptides, differing in one amino acid. The HA-1(His) peptide is currently used for boosting the graft-vs-tumor responses after HLA matched HA-1 mismatched stem cell transplantation; usage of the HA-1(Arg) peptide would significantly enlarge the applicability for this therapy. Our studies on mechanisms causing the HA-1 unidirectional immunogenicity revealed marginal differences in proteasomal digestion, TAP translocation, and binding affinity, whereas both dissociation rates and structural analyses clearly showed marked differences in the stability of these two HLA-A2 bound alleles. These data provide a rationale for the lack of HA-1(Arg) peptide immunogenicity essential for the choice of tumor peptides for stem cell-based immunotherapeutic application.

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