2024/10/19 by Weiwen Zhang, Fernanda Marconi Roversi, Anna B. Morris +9 · 1 voice
Immunology and Microbiology · #Immune Cell Function and Interaction #Immunotherapy and Immune Responses #T-cell and B-cell Immunology
paper · pdf · doi:10.1016/j.ajt.2024.10.011
openalex publication_date 2024/10/19 · openalex created_date 2024/10/20 · openalex updated_date 2026/06/21
The direct alloresponse, pivotal in transplant rejection, occurs when recipient T cells recognize intact allogeneic peptide-major histocompatibility complex (pMHC) complexes. Despite extensive research, our understanding of alloreactive CD8 + T cells against an individual MHC allele in humans remains limited, especially their precursor frequency, MHC specificity, and peptide specificity. By using K562 cell–based artificial antigen-presenting cells expressing human leukocyte antigen (HLA)-A∗01:01, HLA-A∗02:01, or HLA-A∗03:01, we determined that the precursor frequency of alloreactive CD8 + T cells against a single MHC allele ranges from 0.1% to 0.5%. Further, these cells exhibited MHC specificity regarding proliferation, activation, interferon gamma secretion, and cytolytic ability, with limited crossreactivity toward nontargeted MHC alleles. Focusing on anti-A2 alloreactive CD8 + T cells, we developed a peptide-exchangeable artificial antigen-presenting cell that displays selected peptides on HLA-A∗02:01. From a set of 95 computationally curated A2-restricted peptides most abundant in renal tubular cells, we identified 2 immunogenic kidney peptides across multiple donors. Overall, our findings significantly enhance the understanding of direct alloresponse and provide a toolkit for future mechanistic studies and reproducible patient monitoring.