Identification of mimotopes for the H4 minor histocompatibility antigen

Michael A. Strausbauch, Wendy K. Nevala, Derry C. Roopenian, Heather E. Stefanski, Peter J. Wettstein

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The H4 minor histocompatibility antigen (HA) of mice includes a single immunogenic peptide presented by H-2Kb molecules that stimulates skin allograft rejection and is immunodominant in the stimulation of cytolytic T lymphocytes (CTL) specific for multiple minor HA. We have identified H4 mimotopes that are recognized by the H4-specific M9 CTL clone through the use of a random peptide library comprised of bacterial clones expressing an inducible fusion protein tailed with the octamer sequence SXIXFXXL. Eight discrete mimotopes were identified that sensitized RMA-S cells for lysis by M9 CTL down to concentrations of 10-11 M. Comparable reactivity was observed with a short-term, H4-specific CTL line indicating that the mimotopes were not solely specific for the selecting M9 clone. All mimotopes included Gly at p2 and either Val or Ile at p4, suggesting a requirement for a hydrophobic residue with specific conformation. All mimotopes included either Arg or His at p7, implicating a requirement for a specific positively charged amino acid at that position. The sixth position was more variable with four of eight mimotopes having a Val residue with single mimotopes including alternative amino acids, the majority of which were hydrophobic. Analysis of mimotopes for hydrophobicity and charge by reverse-phase HPLC and capillary electrophoresis respectively indicated that (i) mimotopes with Val at both p4 and p6 were hydrophobically similar (but not identical) to the natural H4 peptide, and (ii) a S→E substitution at p1 resulted in a peptide (EGIVFVRL) with charge characteristics equivalent to those of the natural H4 peptide.

Original languageEnglish (US)
Pages (from-to)421-434
Number of pages14
JournalInternational Immunology
Volume10
Issue number4
DOIs
StatePublished - 1998

Fingerprint

Minor Histocompatibility Antigens
T-Lymphocytes
Peptides
Clone Cells
Amino Acids
Peptide Library
Capillary Electrophoresis
Hydrophobic and Hydrophilic Interactions
Allografts
High Pressure Liquid Chromatography
Skin
Proteins

Keywords

  • Cytotoxic T lymphocyte
  • Mimotope
  • Minor histocompatibility antigen

ASJC Scopus subject areas

  • Immunology

Cite this

Strausbauch, M. A., Nevala, W. K., Roopenian, D. C., Stefanski, H. E., & Wettstein, P. J. (1998). Identification of mimotopes for the H4 minor histocompatibility antigen. International Immunology, 10(4), 421-434. https://doi.org/10.1093/intimm/10.4.421

Identification of mimotopes for the H4 minor histocompatibility antigen. / Strausbauch, Michael A.; Nevala, Wendy K.; Roopenian, Derry C.; Stefanski, Heather E.; Wettstein, Peter J.

In: International Immunology, Vol. 10, No. 4, 1998, p. 421-434.

Research output: Contribution to journalArticle

Strausbauch, MA, Nevala, WK, Roopenian, DC, Stefanski, HE & Wettstein, PJ 1998, 'Identification of mimotopes for the H4 minor histocompatibility antigen', International Immunology, vol. 10, no. 4, pp. 421-434. https://doi.org/10.1093/intimm/10.4.421
Strausbauch MA, Nevala WK, Roopenian DC, Stefanski HE, Wettstein PJ. Identification of mimotopes for the H4 minor histocompatibility antigen. International Immunology. 1998;10(4):421-434. https://doi.org/10.1093/intimm/10.4.421
Strausbauch, Michael A. ; Nevala, Wendy K. ; Roopenian, Derry C. ; Stefanski, Heather E. ; Wettstein, Peter J. / Identification of mimotopes for the H4 minor histocompatibility antigen. In: International Immunology. 1998 ; Vol. 10, No. 4. pp. 421-434.
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