{"id":36583,"date":"2025-07-01T11:48:18","date_gmt":"2025-07-01T09:48:18","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/07\/01\/isolation-of-mitochondrial-mutation-specific-t-cell-receptors\/"},"modified":"2025-07-01T11:48:18","modified_gmt":"2025-07-01T09:48:18","slug":"isolation-of-mitochondrial-mutation-specific-t-cell-receptors","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/07\/01\/isolation-of-mitochondrial-mutation-specific-t-cell-receptors\/","title":{"rendered":"Isolation of mitochondrial mutation-specific T cell receptors"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jun 30:vkaf139. doi: 10.1093\/jimmun\/vkaf139. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Neoantigen-specific T cells play a major role in cancer immunotherapy. Mutated proteins derived from non-synonymous mutations in tumor genomic DNA are the major source of neoantigens. It is conceivable that non-synonymous mutations found in tumor mitochondrial DNA (mtDNA) can also generate neoantigens that can be recognized by T cell receptors (TCRs). However, no tumor mitochondrial mutation-specific TCRs have been reported. As a proof-of-concept study, we obtained 3,798 non-synonymous single-nucleotide mutations across 38 tumor types through The Cancer Mitochondria Atlas project. These mutations were subjected to an epitope prediction algorithm to predict binding affinities for HLA-A*0201. The top 300 candidate peptides were synthesized and screened against 10 healthy donors with homozygous HLA-A*0201 alleles. Mutation-reactive T cells were subjected to single-cell sequencing to identify TCR sequences, followed by validations. Here, four MT-ND2 (A103T) mutation-specific TCRs were isolated from a donor. These TCRs interacted with HLA-A*0201-restricted IMMAMTMKL peptide. Additionally, through a single-cell sequencing approach, we demonstrated that a non-synonymous mutation, MT-CO1 (V274I), could be detected in nearly all tumor cells in a colorectal tumor specimen, whereas other mutations in 2 out of 4 tumors were detected in subclonal populations. This study suggests that isolating tumor mitochondrial mutation-specific TCRs is possible, but some biological barriers need to be considered.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40587813\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250701054817&amp;v=2.18.0.post9+e462414\">40587813<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf139\">10.1093\/jimmun\/vkaf139<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jun 30:vkaf139. doi: 10.1093\/jimmun\/vkaf139. Online ahead of print. ABSTRACT Neoantigen-specific T cells play a major role in cancer immunotherapy. Mutated proteins derived from non-synonymous mutations in tumor genomic DNA are the major source of neoantigens. It is conceivable that non-synonymous mutations found in tumor mitochondrial DNA (mtDNA) can also generate neoantigens that &#8230; <a title=\"Isolation of mitochondrial mutation-specific T cell receptors\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/07\/01\/isolation-of-mitochondrial-mutation-specific-t-cell-receptors\/\" aria-label=\"Read more about Isolation of mitochondrial mutation-specific T cell receptors\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-36583","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36583","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=36583"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36583\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=36583"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=36583"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=36583"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}