Faculty Research 1990 - 1999

Title

Identification of mimotopes for the H4 minor histocompatibility antigen.

Document Type

Article

Publication Date

1998

Keywords

Amino Acid Sequence, Animal, Chromatography, High Pressure Liquid, Electrophoresis, Capillary/methods, Epitopes/analysis/immunology/isolation & purification, H-2 Antigens/immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Minor Histocompatibility Antigens/*immunology, Molecular Sequence Data, Peptides/immunology/isolation & purification, T-Lymphocytes, Cytotoxic/immunology

JAX Source

Int Immunol 1998 Apr;10(4):421-34

Grant

AI16052/AI/NIAID

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.

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