HLA-DRB1 Allelic Combinations Differentially Shape Dendritic Cell Antigen Presentation Enhanced by Tumour Cell Line Lysate-Pulsing
Lázaro Bermejo, Gonzalo (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Cedano Rodríguez, Juan Antonio (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Faus Cid, Maitane (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Roura Mir, Carme (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Garrigós Cubells, Laia (Centre Internacional de Càncer de Mama. Barcelona)
Pérez-García, José (Medical Scientia Innovation Research (MedSIR))
Román-García, Javier (Universidad Europea de Madrid)
Cortés Castán, Javier (Medical Scientia Innovation Research (MedSIR))
Aran, Andrea (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Martí, Mercè (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Fecha:	2026
Resumen:	The anti-tumour immune response plays a pivotal role in eliminating tumour cells, with the presence of tumour-infiltrating lymphocytes (TILs) often correlated with improved patient outcomes. Among these, CD4+ T lymphocytes act as key orchestrators of the immune response, functioning as effector and regulatory cells, and are essential for establishing immunological memory. To better understand the role of CD4+ T cells in anti-tumour immunity, we analysed the HLA-II immunopeptidome of dendritic cells (DCs) from HLA-heterozygous donors pulsed with a protein extract from the MCF-7 tumour cell line. Our objective was to identify differences in the arrays of peptides binding distinct HLA-DRB1 allele combinations and the effect of DC pulsing on peptide presentation. We found that presented peptide repertoires are strongly influenced by HLA-DR heterozygosity in an allele-specific manner. Alleles with high binding strength (e. g. , DRB1*01:01, DRB1*03:01 and DRB1*04:04) tended to dominate peptide presentation; however, this dominance is significantly modulated by the allelic combination, suggesting that antigen presentation is shaped not only by individual allele properties but also by their combinations. Pulsing DCs with MCF-7 extracts increased peptide overlap between donors and enabled the identification of 58 proteins putatively derived from the tumour cell line lysates. Interestingly, peptide presentation from these proteins reinforced allele-specific features of dominance and weakness previously observed across the entire immunopeptidome. Gaining insights into the peptide repertoire presented by distinct HLA-DR combinations could inform the design of personalised immunotherapies based on peptide-pulsed DCs, ultimately enhancing CD4+ TIL responses across diverse patient populations.
Ayudas:	Agencia Estatal de Investigación PID2021-125470OB-I00
Nota:	Altres ajuts: acords transformatius de la UAB
Nota:	Altres ajuts: Contigo Contra el Cáncer de la Mujer Foundation (#BREASTILs Project), 'Functional Study of TILs from breast cancer patients: an approach to personalized medicine', by the Fundación de Investigación Oncológica (FERO)
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Antigen presentation ; CD4+ T cells ; Dendritic cells ; Heterozygosity ; HLA-DRB1 alleles ; Peptides
Publicado en:	HLA: Immune Response Genetics, Vol. 107, Num. 2 (February 2026) , art. e70563

DOI: 10.1111/tan.70563

18 p, 4.6 MB

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