Human leukocyte antigen molecular mismatch to risk stratify kidney transplant recipients Purpose of review Stalled drug development and the lack of improvement in long-term graft survival reflect the unmet need for prognostic and predictive biomarkers in transplantation. Although conventional human leukocyte antigen (HLA) mismatch is too imprecise to fulfill this need, HLA molecular mismatch increases the precision in alloimmune risk assessment by quantifying the difference between donors and recipients at the molecular level. Recent findings Within each conventional HLA mismatch, recipients exhibit a wide range of HLA molecular mismatches with their donors. Quantifying HLA molecular mismatch improves the precision of alloimmune risk assessment for de novo donor-specific antibody development (dnDSA). Alloimmune risk categories developed analyzing dnDSA development were also found to correlate with T-cell-mediated rejection, antibody-mediated rejection, and all cause graft loss in adjusted and unadjusted models. Summary All alloimmunity is driven by differences between donors and recipients at the molecular level. HLA molecular mismatch may represent a fast, reproducible, cost-effective, way to improve alloimmune risk assessment at the time of transplantation to move the field towards precision medicine. Correspondence to Chris Wiebe, Canadian Blood Services Building, 312-777 William Avenue, Winnipeg, MB R3E 3R4, Canada. Tel: +1 204 789 1125; e-mail: cwiebe@hsc.mb.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Follicular T-cell regulation of alloantibody formation Purpose of review To summarize recent studies elucidating the roles of follicular T cells in controlling allospecific antibody responses and antibody-mediated rejection (AbMR). Recent findings The field of antibody regulation has provided an in depth identification of the T-cell subsets involved in regulation of antibody responses. In addition, tools have been developed to study these cells during disease. Over the past few years, these strategies have been implemented in the field of transplantation to study the roles of T cells in mediating pathogenic antibody responses. Summary AbMR is largely responsible for long-term graft failure after solid organ transplantation and is induced by allospecific antibodies. In vaccination and infection, antiboody responses are controlled by humoral immunoregulation in which T follicular helper (Tfh) cells promote, and T follicular regulatory (Tfr) cells inhibit, antibody responses. Recent studies have suggested multifaceted roles for follicular T-cell subsets in regulating allospecific antibody responses and AbMR during organ transplantation. In addition, we discuss research priorities for the field to help elucidate mechanisms used by these cells so that new targeted therapeutics can be developed to prevent AbMR in human organ transplantation. Correspondence to Peter T. Sage, Renal Division, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA. Tel: +1 617 525 8002; e-mail: psage@bwh.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.