Highlights d Macaque germline gene inference identifies several hundred novel IGV alleles d Rhesus and cynomolgus macaques display overlapping IGV allelic content d Analysis of macaque IGV germline genes suggests frequent structural variation d Comprehensive IG databases are essential for analysis of somatic hypermutation

Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRs), especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages.

No abstract

The human T cell receptor (TCR) genes are critical for mediating immune responses to pathogens, tumors and regulating self-antigen recognition. A detailed analysis and validation of expressed TCR alpha, beta, gamma, and delta genes in 45 donors from 4 human populations: African, East Asian, South Asian, and European, revealed a total of 175 novel TCR variable and junctional alleles. The majority of novel alleles contained coding changes and were present at widely differing frequencies in the populations, a finding confirmed using DNA samples and sequences from the 1000 Genomes Project. Importantly, we identified three Neanderthal-derived, introgressed TCR regions, including a highly divergent novel TRGV4 variant, present in all archaic assemblies, that was frequent in all modern Eurasian population groups. Our results demonstrate significant variation in TCR genes at both individual and population levels, providing a strong incentive for including allelic variation in studies of TCR function in human biology.

No abstract