Immune reconstitution after human leukocyte antigen (HLA)-mismatched (haploidentical) hematopoietic stem cell transplantation (haplo-HCT) can significantly influence long-term outcomes. The three possible HLA haplotypes after transplantation are: one carried by both the patient and the donor (shared HLA), one by donor only (donor-specific HLA), and one by patient only (host-specific HLA), and the donor T cells remain restricted to one of these three haplotypes. Understanding the presence of donor T cells restricted to each haplotype may provide more detailed insights into post-transplant immune response and potentially provide valuable information for the development of chimeric antigen receptor T cell or T cell receptor T cell constructs. In this study, patients or donors with HLA-A24 or HLA-A2 were tested with HLA-A*24:02- and A*02:01-restricted cytomegalovirus (CMV)-specific tetramers for detecting the respective HLA-restricted T cells. Sixty-four samples from 40 patients were assayed. More than half of the patients at day 90 and all patients by day 900 had shared HLA-restricted T cells. After day 90, half of the patients had donor-specific HLA-restricted T cells, but no host-specific HLA-restricted T cells were found. In the comparative analysis of the transplant types, shared HLA-restricted T cells were positive in all three categories: haplo-HCT (50%), 2-haplo-mis-HCT (75%), and spousal HCT (67%). Furthermore, donor-specific HLA-restricted T cells demonstrated positivity in haplo-HCT at 57% and in 2-haplo-mis-HCT at 60%, with a threshold of 0.01%. Donor-specific HLA-restricted T cells for spousal HCT were not examined due to the lack of an appropriate HLA combination for the tetramers. The presence of shared HLA-restricted T cells explains the host defense after HLA-haploidentical transplantation, while the presence of donor-specific HLA-restricted T cells may account for host defense against hematotropic viruses, such as CMV. However, this study failed to detect host-specific HLA-restricted T cells, leaving the host defense against epitheliotropic viruses unresolved, thus requiring further investigation.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trim.2024.102099DOI Listing

Publication Analysis

Top Keywords

hla-restricted cells
40
donor-specific hla-restricted
16
cells
13
shared hla-restricted
12
host defense
12
hla-restricted
10
cells restricted
8
host-specific hla
8
hematopoietic stem
8
stem cell
8

Similar Publications

Deciphering Antigen Processing Machinery (APM) as One of the Determinants for Responsiveness of Affected Patients towards Anticancer Immunotherapy.

Asian Pac J Cancer Prev

December 2024

Research Center for Vaccine and Drugs, The National Research and Innovation Agency (BRIN), South Tangerang 15310, Republic of Indonesia.

Immunotherapy is one of the rising stars in the field of anticancer regiments. Aimed at reinvigorating immune cytotoxicity, this platform is capable of bulking up memory subsets by which protection against tumors is served. The most commonly applied immunotherapy is immune checkpoint inhibitor (ICIs) which received FDA approval for non-small lung cancer (NSLC) in 2014.

View Article and Find Full Text PDF
Article Synopsis
  • CMV reactivation is a significant health issue for patients who have undergone stem cell or organ transplants, leading to increased risks of illness and death.
  • Three CMV-specific Fab-antibodies (A6, C1, C7) have been developed to bind to particular MHC molecules, showing effectiveness in targeting and destroying CMV-infected cells, especially when used in combination with natural killer (NK) cells.
  • The TCR-like antibodies also demonstrated the ability to activate neutrophils to kill target cells, offering a promising treatment option for patients experiencing or at risk of CMV reactivation, with a broader potential patient application than previous methods.
View Article and Find Full Text PDF

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8 T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8 T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined.

View Article and Find Full Text PDF

A nonadjuvanted HLA-restricted peptide vaccine induced both T and B cell immunity against SARS-CoV-2 spike protein.

Sci Rep

September 2024

Vacino Biotech Co., Ltd., 4F, No. 99, Lane 130, Sec 1, Academia Rd., Nangang District, Taipei, 11571, Taiwan, ROC.

During COVID-19 pandemic, cases of postvaccination infections and restored SARS-CoV-2 virus have increased after full vaccination, which might be contributed to by immune surveillance escape or virus rebound. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides were designed based on the well-conserved S2 region of the SARS-CoV-2 spike protein regardless of rapid mutation and glycosylation hindrance. The UC peptides were characterized for its effect on immune molecules and cells by HLA-tetramer refolding assay for HLA-binding ability, by HLA-tetramer specific T cell assay for engaged cytotoxic T lymphocytes (CTLs) involvement, by HLA-dextramer T cell assay for B cell activation, by intracellular cytokine release assay for polarization of immune response, Th1 or Th2.

View Article and Find Full Text PDF

Immune reconstitution after human leukocyte antigen (HLA)-mismatched (haploidentical) hematopoietic stem cell transplantation (haplo-HCT) can significantly influence long-term outcomes. The three possible HLA haplotypes after transplantation are: one carried by both the patient and the donor (shared HLA), one by donor only (donor-specific HLA), and one by patient only (host-specific HLA), and the donor T cells remain restricted to one of these three haplotypes. Understanding the presence of donor T cells restricted to each haplotype may provide more detailed insights into post-transplant immune response and potentially provide valuable information for the development of chimeric antigen receptor T cell or T cell receptor T cell constructs.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!