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The role of maternal and fetal human leukocyte antigen genotype in immune tolerance and infectious disease susceptibility during pregnancy
Genotypic differences among individuals play a significant role in the development and outcome of pregnancy, either independently or in combination with environmental factors. We will explore the variation and interaction of maternal and fetal HLA genotypes and their consequences for maternal immune adaptation or activation to improve pregnancy care and preventive therapy.
Hypothesis
Team
Prof. Dr. rer. nat.
Tobias Lenz
Principal Investigator
Britta Meyer
PostDoc
Alexej Sinner
PhD student
Diyar Hamidi
PhD student
Project-related publications
Lenz, T.L. HLA Genes: A hallmark of functional genetic variation and complex evolution. In: Boegel, S. (ed). HLA Typing: Methods and Protocols. Springer US: New York, NY, 2024, pp 1-18. https://doi.org/10.1007/978-1-0716-3874-3_1
Lenz, T.L. Uterine selection for immunocompetent offspring. Proc Natl Acad Sci USA 108, E253 (2011). https://doi.org/10.1073/pnas.1107082108
Lenz, T.L. et al. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases. Nat Genet 47, 1085-1090 (2015). https://doi.org/10.1038/ng.3379
Pierini, F. & Lenz, T.L. Divergent allele advantage at human MHC genes: signatures of past and ongoing selection. Mol Biol Evol 35, 2145-2158 (2018). https://doi.org/10.1093/molbev/msy116
Özer, O. & Lenz, T.L. Unique Pathogen Peptidomes Facilitate Pathogen-Specific Selection and Specialization of MHC Alleles. Mol Biol Evol 38, 4376-4387 (2021). https://doi.org/10.1093/molbev/msab176
Lenz, T.L., Spirin, V., Jordan, D.M. & Sunyaev, S.R. Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection. Mol Biol Evol 33, 2555-2564 (2016). https://doi.org/10.1093/molbev/msw127
Lenz, T.L., Hafer, N., Samonte, I.E., Yeates, S.E. & Milinski, M. Cryptic haplotype-specific gamete selection yields offspring with optimal MHC immune genes. Evolution 72, 2478-2490 (2018). https://doi.org/10.1111/evo.13591