Two Human Monoclonal HLA-Reactive Antibodies Cross-React with Mamu-B*008, a Rhesus Macaque MHC Allotype Associated with Control of Simian Immunodeficiency Virus Replication

J Immunol. 2021 Apr 15;206(8):1957-1965. doi: 10.4049/jimmunol.2001405. Epub 2021 Mar 10.

Abstract

MHC class I molecules play an important role in adaptive immune responses against intracellular pathogens. These molecules are highly polymorphic, and many allotypes have been characterized. In a transplantation setting, a mismatch between MHC allotypes may initiate an alloimmune response. Rhesus macaques (Macaca mulatta, Mamu) are valuable as a preclinical model species in transplantation research as well as to evaluate the safety and efficacy of vaccine candidates. In both lines of research, the availability of nonhuman primate MHC-reactive mAbs may enable in vitro monitoring and detection of presence of particular Mamu molecules. In this study, we screened a collection of thoroughly characterized HLA class I-specific human mAbs for cross-reactivity with rhesus macaque MHC class I allotypes. Two mAbs, OK4F9 and OK4F10, recognize an epitope that is defined by isoleucine (I) at amino acid position 142 that is present on the Indian rhesus macaque Mamu-B*008:01 allotype, which is an allotype known to be associated with elite control of SIV replication. The reactive pattern of a third mAb, MUS4H4, is more complex and includes an epitope shared on Mamu-A2*05:01 and -B*001:01-encoded Ags. This is the first description, to our knowledge, of human HLA-reactive mAbs that can recognize Mamu allotypes, and these can be useful tools for in vitro monitoring the presence of the relevant allelic products. Moreover, OK4F9 and OK4F10 can be powerful mAbs for application in SIV-related research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / genetics
  • Acquired Immunodeficiency Syndrome / immunology*
  • Alleles
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Cross Reactions
  • Genetic Predisposition to Disease
  • HIV-1 / physiology*
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunoglobulin Allotypes
  • K562 Cells
  • Macaca mulatta
  • Polymorphism, Genetic
  • Simian Acquired Immunodeficiency Syndrome / genetics
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / physiology*
  • Virus Replication

Substances

  • Antibodies, Monoclonal
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Immunoglobulin Allotypes