Memory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant. T cells are critical in controlling SARS-CoV-2 infection. The hypermutated BA.2.86 variant exhibits a range of mutations in the spike protein, potentially facilitating evasion from cellular immunity. Müller et al. demonstrate preserved and functional T cell cross-recognition of mutated BA.2.86 epitopes in healthy individuals and patients with chronic lymphocytic leukemia. SARS-CoV-2 spike-specific T cells are profiled in healthy individuals and CLL patients. T cell cross-recognition of mutated BA.2.86 spike epitopes is largely preserved. BA.2.86-reactive T cells display features of high functional capacity. The BA.2.86 variant of SARS-CoV-2 was first detected in July 2023 in Denmark and soon classified as a variant under monitoring by the World Health Organization. As of December 2023, BA.2.86 and the closely related JN.1 sublineage are rapidly spreading on a global scale, supplanting XBB as the predominant variant of SARS-CoV-2. Whole-genome sequencing identified a total of 122 mutations relative to the Wu-Hu.1 reference genome, and 79 of these mutations were present in the spike protein. In comparison with the currently circulating BA.2 and XBB sub-variants, BA.2.86 harbors more than 30 additional spike mutations. BA.2.86 poses challenges since the large number of mutations likely supports increased immune evasion. Early studies in September 2023 suggested that, albeit having lower infectivity, BA.2.86 would still have greater fitness compared with the currently circulating XBB subvariants due to an increased resistance to humoral immunity. Furthermore, it was shown that BA.2.86 is resistant to clinically relevant monoclonal antibodies. More recent studies indicate that neutralizing antibody titers against BA.2.86 are comparable to titers against the currently circulating XBB sublineages. This is problematic due to the important role of neutralizing antibodies in protection from infection and severe disease. Yet, compiled evidence, for instance, from B cell-deficient patients or animal models, suggests that memory T cell responses can step in and provide protection from severe disease in the absence of B cell responses. Whereas the extent of BA.2.86's ability to evade humoral immunity seems to be still under debate, there is, to date, a complete lack of T cell immunity data. Hence, we set out to investigate T cell responses to BA.2.86 in both immunocompetent healthy controls (HCs) and individuals with chronic lymphocytic leukemia (CLL), a patient group that responded poorly to initial vaccine doses and displayed particularlyMemory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant. T cells are critical in controlling SARS-CoV-2 infection. The hypermutated BA.2.86 variant exhibits a range of mutations in the spike protein, potentially facilitating evasion from cellular immunity. Müller et al. demonstrate preserved and functional T cell cross-recognition of mutated BA.2.86 epitopes in healthy individuals and patients with chronic lymphocytic leukemia. SARS-CoV-2 spike-specific T cells are profiled in healthy individuals and CLL patients. T cell cross-recognition of mutated BA.2.86 spike epitopes is largely preserved. BA.2.86-reactive T cells display features of high functional capacity. The BA.2.86 variant of SARS-CoV-2 was first detected in July 2023 in Denmark and soon classified as a variant under monitoring by the World Health Organization. As of December 2023, BA.2.86 and the closely related JN.1 sublineage are rapidly spreading on a global scale, supplanting XBB as the predominant variant of SARS-CoV-2. Whole-genome sequencing identified a total of 122 mutations relative to the Wu-Hu.1 reference genome, and 79 of these mutations were present in the spike protein. In comparison with the currently circulating BA.2 and XBB sub-variants, BA.2.86 harbors more than 30 additional spike mutations. BA.2.86 poses challenges since the large number of mutations likely supports increased immune evasion. Early studies in September 2023 suggested that, albeit having lower infectivity, BA.2.86 would still have greater fitness compared with the currently circulating XBB subvariants due to an increased resistance to humoral immunity. Furthermore, it was shown that BA.2.86 is resistant to clinically relevant monoclonal antibodies. More recent studies indicate that neutralizing antibody titers against BA.2.86 are comparable to titers against the currently circulating XBB sublineages. This is problematic due to the important role of neutralizing antibodies in protection from infection and severe disease. Yet, compiled evidence, for instance, from B cell-deficient patients or animal models, suggests that memory T cell responses can step in and provide protection from severe disease in the absence of B cell responses. Whereas the extent of BA.2.86's ability to evade humoral immunity seems to be still under debate, there is, to date, a complete lack of T cell immunity data. Hence, we set out to investigate T cell responses to BA.2.86 in both immunocompetent healthy controls (HCs) and individuals with chronic lymphocytic leukemia (CLL), a patient group that responded poorly to initial vaccine doses and displayed particularly