3ft3 Citations

Steric hindrance and fast dissociation explain the lack of immunogenicity of the minor histocompatibility HA-1Arg Null allele.

Abstract

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.

Articles - 3ft3 mentioned but not cited (1)

  1. Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope. Song I, Gil A, Mishra R, Ghersi D, Selin LK, Stern LJ. Nat Struct Mol Biol 24 395-406 (2017)


Reviews citing this publication (10)

  1. Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia. Bleakley M, Riddell SR. Immunol Cell Biol 89 396-407 (2011)
  2. TCR Recognition of Peptide-MHC-I: Rule Makers and Breakers. Szeto C, Lobos CA, Nguyen AT, Gras S. Int J Mol Sci 22 E68 (2020)
  3. Minor histocompatibility antigens: past, present, and future. Spierings E. Tissue Antigens 84 374-360 (2014)
  4. Understanding the complexity and malleability of T-cell recognition. Miles JJ, McCluskey J, Rossjohn J, Gras S. Immunol Cell Biol 93 433-441 (2015)
  5. TCR-Like CAR-T Cells Targeting MHC-Bound Minor Histocompatibility Antigens. Akatsuka Y. Front Immunol 11 257 (2020)
  6. Minor Histocompatibility Antigen-Specific T Cells. Summers C, Sheth VS, Bleakley M. Front Pediatr 8 284 (2020)
  7. Augmentation of anti-tumor immunity by adoptive T-cell transfer after allogeneic hematopoietic stem cell transplantation. Bleakley M, Turtle CJ, Riddell SR. Expert Rev Hematol 5 409-425 (2012)
  8. Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery. de Sousa E, Lérias JR, Beltran A, Paraschoudi G, Condeço C, Kamiki J, António PA, Figueiredo N, Carvalho C, Castillo-Martin M, Wang Z, Ligeiro D, Rao M, Maeurer M. Front Immunol 12 592031 (2021)
  9. Tumor vaccines and beyond. Melenhorst JJ, Barrett AJ. Cytotherapy 13 8-18 (2011)
  10. The Connection Between Minor H Antigens and Neoantigens and the Missing Link in Their Prediction. Mutis T, Xagara A, Spaapen RM. Front Immunol 11 1162 (2020)

Articles citing this publication (11)