Minor histocompatibility antigens (mHA) are small segments of proteins, called peptides, that reside on the surface of cells. They are diverse and consist of short amino acid sequences. CD8+ T cells specific to an mHA can target cells expressing that particular mHA. Leukemic cells, therefore, can become targets of specific CD8+ T cells, known as graft-versus-leukemia (GVL).
However, epithelial cells also have mHA expression, and targeting from CD8+ T cells can lead to graft-versus-host disease (GVHD).
At the 2023 Tandem Meetings of ASTCT and CIBMTR held from February 15-19 in Orlando, Florida, researcher Othmane Jadi from the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, presented results of a study that sought to determine whether these 2 outcomes, GVL and GVHD, are mediated by a combination of mHA from a donor-recipient pair (DRP) or individual-level immunodominant mHAs.
Jadi et al hypothesized, “an increased mHA count and individual mHAs would be associated with lower relapse and disease-related mortality (DRM) and/or increased GvHD mortality.”
To test their hypothesis, the team used the DISCOVeRY-BMT dataset to identify 2249 European American DRPs treated for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with allogeneic hematopoietic cell transplantation (alloHCT). After determining both the mHAs present in DRPs and mHAs most likely to be immunogenic, the researchers looked at the association of both with 1-year outcomes.
Per their published abstract, “Patients with a class I mHA count greater than the population median had a 39%…increase in hazard of GvHD mortality compared to those with a count less than the median.”
They also identified several individual mHAs associated with increased GvHD mortality risk and DRM in individuals with specific HLA-binding affinities.
“Our study reports the first large scale investigation of the associations of predicted class I and class II mHA peptides with clinical outcomes following alloHCT,” Jadi et al concluded, adding, “We identified both expected and unexpected relationships between mHA count/individual mHAs with various outcomes.”
Jadi O, Tang H, Olsen K, et al. Associations of minor histocompatibility antigens with clinical outcomes following allogenic hematopoietic cell transplantation. Abstract #31. Presented at the 2023 Tandem Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL.
