A normal female donor (H9) is described, whose cells generate strong cytotoxicity against a human minor histocompatibility antigen in vitro. These cytotoxic T lymphocytes are generated after secondary restimulation with cells from an HLA-A, -B, -C, and -DR-matched donor and are HLA restricted (HLA-B7). No other donor could be identified whose cells responded to this antigen. The two children of donor H9 are virtually HLA identical to her and one of the children expresses the relevant minor histocompatibility antigen. These data suggest that priming in vivo during pregnancy has facilitated cytotoxic T cell response to human minor histocompatibility antigens in vitro.

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Possible immunogenic heterogeneity of the HLA-Bw44 antigen was investigated using cytotoxic T lymphocytes (CTL) generated between donors identical for HLA-A2,3,-B7,w44. Highly discriminatory CTL combinations were identified that defined two subgroups of Bw44, designated 44.1 and 44.2. Out of 47 Bw44-positive donors tested in a population study, 30 were lysed by the CTL defining 44.1, and 19 were lysed by the CTL defining 44.2. All Bw44 cells could be typed as either 44.1 or 44.2, except two Bw44-positive cells that were phenotypically homozygous for the serologically defined Bw44 antigen and were lysed by both CTL. No Bw44-negative donors (zero out of 37) expressed either 44.1 or 44.2, although cold target blocking was required to eliminate a contaminating reactivity of one CTL population on Bw35 and some Bw45 cells. CTL were also raised between responder/stimulator combinations mismatched for Bw44. These CTL lysed all Bw44-positive target cells, indicating a CML antigen shared by all Bw44 cells. But clear discrimination of the 44.1 and 44.2 subgroups was obtained when appropriate cold target blocking cells were added. All donors with 44.2 expressed high levels of serologically detectable Bw44 on their platelets, and all with 44.1 expressed low levels (p less than 0.005). Furthermore, population studies indicate that 44.1 is in positive linkage disequilibrium with HLA-A2 and possibly DR4, whereas 44.2 is in positive linkage disequilibrium with HLA-DR7 and possibly HLA-A23, -A26, and -A29. These data suggest the existence of two genetically and functionally different subgroups of Bw44 antigens.

Neutral proteases can be released from PMN neutrophils in blood smears from healthy subjects by incubation with NaCl-borate buffer. The activity of the PMN proteases can be revealed by the degradation of erythrocytes and plasma within ring-shaped areas centered around each neutrophil (halo effect). During the acute stage of various inflammatory diseases (pneumonia, meningitis, cholecystitis, etc.) the activity of neutral PMN proteases is substantially reduced, as reflected by reduced halo formation. After recovery, halo formation returns to normal. Temporary lowering of neutral PMN proteases is thus one of a series of functional defects of PMN neutrophils which are detectable in the course of acute infectious diseases. These include reduced phagocytosis, altered chemotaxis and reduced bactericidal function. The cytochemical test for neutrophilic granulocyte function used in the present investigation is especially practical by comparison with the other techniques: it saves time and is simple to perform.

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